Publications

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2023
Parylene C as a Multipurpose Material for Electronics and Microfluidics, Coelho, {Beatriz J. }, Pinto {Joana V. }, Martins Jorge, Rovisco Ana, Barquinha Pedro, Fortunato Elvira, Baptista {Pedro V. }, Martins Rodrigo, and Igreja Rui , Polymers, may, Volume 15, Number 10, (2023) Abstract

Poly(p-xylylene) derivatives, widely known as Parylenes, have been considerably adopted by the scientific community for several applications, ranging from simple passive coatings to active device components. Here, we explore the thermal, structural, and electrical properties of Parylene C, and further present a variety of electronic devices featuring this polymer: transistors, capacitors, and digital microfluidic (DMF) devices. We evaluate transistors produced with Parylene C as a dielectric, substrate, and encapsulation layer, either semitransparent or fully transparent. Such transistors exhibit steep transfer curves and subthreshold slopes of 0.26 V/dec, negligible gate leak currents, and fair mobilities. Furthermore, we characterize MIM (metal–insulator–metal) structures with Parylene C as a dielectric and demonstrate the functionality of the polymer deposited in single and double layers under temperature and AC signal stimuli, mimicking the DMF stimuli. Applying temperature generally leads to a decrease in the capacitance of the dielectric layer, whereas applying an AC signal leads to an increase in said capacitance for double-layered Parylene C only. By applying the two stimuli, the capacitance seems to suffer from a balanced influence of both the separated stimuli. Lastly, we demonstrate that DMF devices with double-layered Parylene C allow for faster droplet motion and enable long nucleic acid amplification reactions.

2020
Porphyrin Pigments in Polychaeta: Explorations on the Evolution of Haem Metabolism in Marine Eumetazoans, Martins, C., Rodrigo {A. P. }, Madeira C., D'Ambrosio M., Goncalves C., Parola {A. J. }, Grosso {A. R. }, Baptista {P. V. }, Fernandes {A. R. }, and Costa {P. M. } , jan, Volume 18, (2020) Abstract
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2019
Paper-Based SERS Platform for One-Step Screening of Tetracycline in Milk, Marques, Ana, Veigas Bruno, Araújo Andreia, Pagará Beatriz, Baptista {Pedro Viana}, Águas Hugo, Martins Rodrigo, and Fortunato Elvira , Scientific Reports, dec, Volume 9, Number 1, (2019) Abstract

Throughout the last decade, the expansion of food testing has been gradually moving towards ordinary high throughput screening methods performed on-site. The demand for point-of-care testing, able to distinguish molecular signatures with high accuracy, sensitivity and specificity has been significantly increasing. This new requirement relies on the on-site detection and monitorization of molecular signatures suitable for the surveillance of food production and processing. The widespread use of antibiotics has contributed to disease control of livestock but has also created problems for the dairy industry and consumers. Its therapeutic and subtherapeutic use has increased the risk of contamination in milk in enough concentrations to cause economic losses to the dairy industry and have a health impact in highly sensitive individuals. This study focuses on the development of a simple Surface-Enhanced Raman Spectroscopy (SERS) method for fast high throughput screening of tetracycline (TET) in milk. For this, we integrate a paper-based low-cost, fully recyclable and highly stable SERS platform, with a minimal sample preparation protocol. A two-microliter sample of milk solutions spiked with TET (from 0.01 to 1000 ppm) is dried on a silver nanoparticle coated cardboard substrate and measured via a Raman spectrophotometer. The SERS substrate showed to be extremely stable with a shelf life of several months. A global spectrum principal component analysis approach was used to test all the detected vibrational modes and their correlation with TET concentration. Peak intensity ratios (455 cm−1/1280 cm−1 and 874 cm−1/1397 cm−1) were found to be correlated with TET concentrations in milk, achieving a sensitivity as low as 0.1 ppm. Results indicate that this SERS method combined with portable Raman spectrometer is a potential tool that can be used on-site for the monitoring of TET residues and other antibiotics.

2018
POxylated Dendrimer-Based Nano-in-Micro Dry Powder Formulations for Inhalation Chemotherapy, Restani, {Rita B. }, Pires {Rita F. }, Tolmatcheva Anna, Cabral Rita, Baptista {Pedro V. }, Fernandes {Alexandra R. }, Casimiro Teresa, Bonifácio {Vasco D. B. }, and Aguiar-Ricardo Ana , ChemistryOpen, oct, Volume 7, Number 10, p.772–779, (2018) Abstract

POxylated polyurea dendrimer (PUREG4OOx48)-based nanoparticles were loaded with paclitaxel (PTX) and doxorubicin (DOX) and micronized with chitosan (CHT) by using supercritical CO2-assisted spray drying (SASD). Respirable, biocompatible, and biodegradable dry powder formulations (DPFs) were produced to effectively transport and deliver the chemotherapeutics with a controlled rate to the deep lung. In vitro studies performed with the use of the lung adenocarcinoma cell line showed that DOX@PUREG4OOx48 nanoparticles were much more cytotoxic than the free drug. Additionally, the DPFs did not show higher cytotoxicity than the respective nanoparticles, and DOX-DPFs showed a higher chemotherapeutic effect than PTX formulations in adenocarcinoma cells.

2017
Photothermal enhancement of chemotherapy in breast cancer by visible irradiation of Gold Nanoparticles, Mendes, Rita, Pedrosa Pedro, Lima {João C. }, Fernandes {Alexandra R. }, and Baptista {Pedro V. } , Scientific Reports, sep, Volume 7, Number 1, (2017) Abstract

Photothermal Therapy (PTT) impact in cancer therapy has been increasing due to the enhanced photothermal capabilities of a new generation of nanoscale photothermal agents. Among these nanoscale agents, gold nanoshells and nanorods have demonstrated optimal properties for translation of near infra-red radiation into heat at the site of interest. However, smaller spherical gold nanoparticles (AuNPs) are easier to produce, less toxic and show improved photoconversion capability that may profit from the irradiation in the visible via standard surgical green lasers. Here we show the efficient light-to-heat conversion of spherical 14 nm AuNPs irradiated in the visible region (at the surface plasmons resonance peak) and its application to selectively obliterate cancer cells. Using breast cancer as model, we show a synergistic interaction between heat (photoconversion at 530 nm) and cytotoxic action by doxorubicin with clear advantages to those of the individual therapy approaches.

Potentiating angiogenesis arrest in vivo via laser irradiation of peptide functionalised gold nanoparticles, Pedrosa, Pedro, Heuer-Jungemann Amelie, Kanaras {Antonios G. }, Fernandes {Alexandra R. }, and Baptista {Pedro V. } , Journal of Nanobiotechnology, nov, Volume 15, Number 1, (2017) Abstract

Background: Anti-angiogenic therapy has great potential for cancer therapy with several FDA approved formulations but there are considerable side effects upon the normal blood vessels that decrease the potential application of such therapeutics. Chicken chorioallantoic membrane (CAM) has been used as a model to study angiogenesis in vivo. Using a CAM model, it had been previously shown that spherical gold nanoparticles functionalised with an anti-angiogenic peptide can humper neo-angiogenesis. Results: Our results show that gold nanoparticles conjugated with an anti-angiogenic peptide can be combined with visible laser irradiation to enhance angiogenesis arrest in vivo. We show that a green laser coupled to gold nanoparticles can achieve high localized temperatures able to precisely cauterize blood vessels. This combined therapy acts via VEGFR pathway inhibition, leading to a fourfold reduction in FLT-1 expression. Conclusions: The proposed phototherapy extends the use of visible lasers in clinics, combining it with chemotherapy to potentiate cancer treatment. This approach allows the reduction of dose of anti-angiogenic peptide, thus reducing possible side effects, while destroying blood vessels supply critical for tumour progression.

2016
Precision nanomedicine in cancer: how far are we from personalization?, Baptista, {Pedro Viana} , Expert Review of Precision Medicine and Drug Development, may, Volume 1, Number 3, p.227–228, (2016) Abstract
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Peptide-coated gold nanoparticles for modulation of angiogenesis in vivo, Roma-Rodrigues, Catarina, Heuer-Jungemann Amelie, de Fernandes {Maria Alexandra Núncio Carvalho Ramos}, Kanaras {Antonios G. }, and Baptista {Pedro Miguel Ribeiro Viana} , International journal of nanomedicine, Volume 11, p.2633–2639, (2016) Abstract

In this work, peptides designed to selectively interact with cellular receptors involved in the regulation of angiogenesis were anchored to oligo-ethylene glycol-capped gold nanoparticles (AuNPs) and used to evaluate the modulation of vascular development using an ex ovo chick chorioallantoic membrane assay. These nanoparticles alter the balance between naturally secreted pro- and antiangiogenic factors, under various biological conditions, without causing toxicity. Exposure of chorioallantoic membranes to AuNP-peptide activators of angiogenesis accelerated the formation of new arterioles when compared to scrambled peptide-coated nanoparticles. On the other hand, antiangiogenic AuNP-peptide conjugates were able to selectively inhibit angiogenesis in vivo. We demonstrated that AuNP vectorization is crucial for enhancing the effect of active peptides. Our data showed for the first time the effective control of activation or inhibition of blood vessel formation in chick embryo via AuNP-based formulations suitable for the selective modulation of angiogenesis, which is of paramount importance in applications where promotion of vascular growth is desirable (eg, wound healing) or ought to be contravened, as in cancer development.

2015
POxylated Polyurea Dendrimers: Smart Core-Shell Vectors with IC50 Lowering Capacity, Restani, {Rita B. }, Conde João, Pires {Rita F. }, Martins Pedro, Fernandes {Alexandra R. }, Baptista {Pedro V. }, Bonifacio {Vasco D. B. }, and Aguiar-Ricardo Ana , Macromolecular Bioscience, aug, Volume 15, Number 8, p.1045–1051, (2015) Abstract

The design and preparation of highly efficient drug delivery platforms using green methodologies is at the forefront of nanotherapeutics research. POxylated polyurea dendrimers are efficiently synthesized using a supercritical-assisted polymerization in carbon dioxide. These fluorescent, pH-responsive and water-soluble core-shell smart nanocarriers show low toxicity in terms of cell viability and absence of glutathione depletion, two of the major side effect limitations of current vectors. The materials are also found to act as good transfection agents, through a mechanism involving an endosomal pathway, being able to reduce 100-fold the IC50 of paclitaxel.

2014
Polyurea dendrimer for efficient cytosolic siRNA delivery, Restani, {Rita B. }, Conde João, Baptista {Pedro V. }, Cidade {Maria Teresa}, Bragan{\c c}a {Ana M. }, Morgado Jorge, Correia {Ilídio J. }, Aguiar-Ricardo Ana, and Bonifácio {Vasco D. B. } , RSC Advances, Volume 4, Number 97, p.54872–54878, (2014) Abstract

The design of small interfering RNA (siRNA) delivery materials showing efficacy in vivo is at the forefront of nanotherapeutics research. Polyurea (PURE-type) dendrimers are 'smart' biocompatible 3D polymers that unveil a dynamic and elegant back-folding mechanism involving hydrogen bonding between primary amines at the surface and tertiary amines and ureas at the core. Similarly, to a biological proton pump, they are able to automatically and reversibly transform their conformation in response to pH stimulus. Here, we show that PURE-G4 is a useful gene silencing platform showing no cellular toxicity. As a proof of concept we investigated the PURE-G4-siRNA dendriplex, which was shown to be an attractive platform with high transfection efficacy. The simplicity associated with the complexation of siRNA with polyurea dendrimers makes them a powerful tool for efficient cytosolic siRNA delivery.

A promising road with challenges: where are gold nanoparticles in translational research?, Bao, Chenchen, Conde João, Polo Ester, {del Pino} Pablo, Moros Maria, Baptista Pedro, Grazu Valeria, Cui Daxiang, and {de la Fuente} {Jesus M. } , Nanomedicine, Volume 9, Number 15, p.2353–2370, (2014) Abstract

Nanoenabled technology holds great potential for health issues and biological research. Among the numerous inorganic nanoparticles that are available today, gold nanoparticles are fully developed as therapeutic and diagnostic agents both in vitro and in vivo due to their physicochemical properties. Owing to this, substantial work has been conducted in terms of developing biosensors for noninvasive and targeted tumor diagnosis and treatment. Some studies have even expanded into clinical trials. This article focuses on the fundamentals and synthesis of gold nanoparticles, as well as the latest, most promising applications in cancer research, such as molecular diagnostics, immunosensors, surface-enhanced Raman spectroscopy and bioimaging. Challenges to their further translational development are also discussed.

2013
Plastic Compatible Sputtered Ta2O5 Sensitive Layer for Oxide Semiconductor TFT Sensors, Branquinho, Rita, {Vaz Pinto} Joana, Busani {Tito Livio}, Barquinha {Pedro Miguel Cândido}, Pereira {Luis Miguel Nunes}, Baptista {Pedro Miguel Ribeiro Viana}, de Martins {Rodrigo Ferrão Paiva}, and Fortunato {Elvira Maria Correia} , Journal Of Display Technology, sep, Volume 9, Number 9, p.723–728, (2013) Abstract

The effect of post-deposition annealing temperature on the pH sensitivity of room temperature RF sputtered Ta2O5 was investigated. Structural and morphological features of these films were analyzed before and after annealing at various temperatures. The deposited films are amorphous up to 600 degrees C and crystallize at 700 degrees C in an orthorhombic phase. Electrolyte-insulator-semiconductor (EIS) field effect based sensors with an amorphous Ta2O5 sensing layer showed pH sensitivity above 50 mV/pH. For sensors annealed above 200 degrees C pH sensitivity decreased with increasing temperature. Stabilized sensor response and maximum pH sensitivity was achieved after low temperature annealing at 200 degrees C, which is compatible with the use of polymeric substrates and application as sensitive layer in oxides TFT-based sensors.

2011
Portable optoelectronic biosensing platform for identification of mycobacteria from the Mycobacterium tuberculosis complex, Silva, {Leonardo Bione}, Veigas Bruno, c}alo Doria Gon{\c, Costa Pedro, Inácio João, Martins Rodrigo, Fortunato Elvira, and Baptista {Pedro Viana} , Biosensors & Bioelectronics, jan, Volume 26, Number 5, p.2012–2017, (2011) Abstract

In this paper we report on the fabrication and performance of a portable and low cost optoelectronic platform integrating a double color tuned light emitting diode as light source, an amorphous/nanocrystalline silicon photodetector with a flat spectral response in the wavelength range from 520. nm to 630. nm and integrated electronic for signal acquisition and conditioning constituted by current to voltage converter, a filter and an amplification stage, followed by an analog to digital converter, with appropriate software for full automation to minimize human error. Incorporation of the double color tuned light emitting diode provides for a simple yet innovative solution to signal acquisition independently from the light intensity and/or solution concentration, while considerably decreasing production costs. Detection based on Au-nanoprobes constitutes the biorecognition step and allowed identification of specific sequences of Mycobacterium tuberculosis complex, namely Mycobacterium bovis and M. tuberculosis in biological samples.

2010
PH effect on the photochemistry of 4-methylcoumarin phosphate esters: caged-phosphate case study, Pinheiro, {André Vidal}, Parola Jorge} {A., Baptista {Pedro V. }, and Lima {J. C. } , Journal of Physical Chemistry A, dec, Volume 114, Number 49, p.12795–12803, (2010) Abstract

There are numerous reports of coumarin ester derivatives, in particular phosphate esters, as photocleavable cages in biological systems. Despite the comprehensive analysis of the photocleavage mechanism, studies of 4-methylcoumarin caged phosphates and/or nucleotides were always performed at constant pH. In this work, we present the study of the pH effect on the photochemistry of (7-diethylaminocoumarin-4-yl)methyl phosphate (DEACM-P). Fluorescence and photocleavage quantum yields, as well as the fluorescence decay times were measured as a function of the pH. It was found that the pH produces significant changes in the overall photochemical quantum yield of DEACM-P, and the observed changes are complementary to those obtained from the fluorescence quantum yield. Deprotonation of DEACM-HPO4 - to yield DEACM-PO4 2-, produces a decrease in the photochemical quantum yield (from 0.0045 to 0.0003) and an increase in the fluorescence quantum yield (from 0.072 to 0.092). Moreover, from the analysis of the decay times, we have also found that hydroxyl ion is not only relevant, but it is mechanistically involved in the photoreaction of DEACM-HPO4 -.

2005
Principles in genetic risk assessment., Baptista, {Pedro Miguel Ribeiro Viana} , Ther Clin Risk Manag, jan, Volume 1, Number 1, p.15–20, (2005) Abstract
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