berg 2013
DESCRIPTION
Annual report of the activities of the Bioengineering Research Group of the Institute for Biotechnology and Bioengineering (Lisbon, Portugal), year 2013.TRANSCRIPT
2013
Annual Report
BERG | BioEngineering Research Group
Contents
04
About BERG
06 Executive Summary
07 The Research Group
08 Main Indicators
10
Research Activities
12 Bioprocess Engineering and
Biocatalysis Laboratory
14 Bioseparation Engineering Laboratory
16 Biosystems Engineering Laboratory
18 Molecular Bioengineering Laboratory
20 Stem Cell Bioengineering and
Regenerative Medicine Laboratory
24
Research Team
26 Full Professors
28 Associate Professors
30 Assistant Professors
37 Research Scientists
42
Scientific Output
44 Articles
45 Proceedings
46 Books
46 Book Chapters
46 Patents
46 Invited Oral Communications
47 Oral Communications
48 Poster Communications
51 Dissertations
About BERG
2013 BERG Annual Report
Executive Summary
The Research Group
Main Indicators
This report highlights the activities of the research
thrust areas and laboratories of BERG within the
Associated Laboratory Institute for Biotechnology
and Bioengineering.
The major activities in the Bioprocess Engineering
and Biocatalysis Laboratory (BEBL) included the
design of continuous flow systems for enzymatic
catalysis and the design of resilient PVA-based
matrices for entrapment of enzymes, with applica-
tions in the production of sweeteners and cellobi-
ose hydrolysis; and the adaptation of strains to
extreme conditions and their application in bio-
technological processes such as siderophore pro-
duction and bioremediation of hydrocarbons
The Bioseparation Engineering Laboratory
(BEL) in collaboration with Bayer Technology
Services demonstrated the feasibility of scaling-
up the continuous aqueous two-phase extrac-
tion of human antibodies from animal cell cul-
ture supernatants using a battery of mixer-
settlers. Stimuli-responsive cation-exchange
magnetic nanoparticles were also successfully
used to purify a monoclonal antibody from a
CHO cell culture supernatant, allowing a high
clearance of host cell proteins.
The main research topics at BioSystems Engi-
neering Laboratory (BSEL) were focused on
developing and demonstrating the industrial
feasibility of near-infrared spectroscopic for in-
situ multiparametric and reliable monitoring
within PAT, of small and large biomolecules’
manufacturing processes.
The Molecular Bioengineering Laboratory (MBL)
continued its efforts to develop integrated process-
es for the production and purification of plasmids
and minicircles by combining E. coli strain engi-
neering, tailored vector modifications and up-
stream and downstream processing strategies.
Microfluidic-based devices were also demonstrat-
ed for the detection of ochratoxin A and for the
trapping of E. coli cells by dielectrophoresis, and
biomimetic ligands were used to selectively bind
IgG molecules and stabilise proteins.
In the Stem Cell Bioengineering and Regenerative
Medicine Laboratory, (SCBL) a comparative study
of the proliferative and regenerative potential of
bone marrow mesenchymal stem/stromal cells
collected from healthy donors and acute myocardi-
al infarcted (AMI) patients was performed in col-
laboration with Department of Cardiology, Hospital
Santa Marta, Lisboa; and a novel bioprocess inte-
grating the serum-free and feeder-free expansion
and neural commitment of human iPSC and the
depletion of the remaining hiPSC through magnet-
ic-activated cell sorting (MACS) was successfully
developed.
Joaquim M.S. Cabral
BERG Head and Director of IBB
Executive Summary
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The Research Group
BEBL BEL BSEL MBL SCBL
The BioEngineering Research Group (BERG) is a research unit in engineering and life
sciences at the Centre for Biological and Chemical Engineering (CEBQ). CEBQ is the
leading Centre of the Associated Laboratory Institute for Biotechnology and Bioengi-
neering (IBB), a network of research centres across Portugal. IBB has been identified
by the Portuguese Ministry of Science, Technology and Higher Education as a strate-
gic infrastructure for the development of the Portuguese R&D and innovation policies
in the areas of Biotechnology, Bioengineering, Life, Biomedical and Agricultural Sci-
ences. BERG activities within the Associated Laboratory IBB are focused on the The-
matic Areas of Industrial and Environmental Biotechnology/Bioenergy, Health Biotech-
nology and Nanobiotechnology.
BERG aims at excellence in research and advanced education in biotechnology and
bioengineering. The overall goal is to contribute for a better understanding of the
mechanisms that occur at the molecular and cellular levels, in order to translate them
into rational applications of biological systems relevant to the Industrial and Health
care sectors. BERG research priorities have special emphasis on Bioprocess and Bio-
systems Engineering, Molecular Bioengineering, Nanobiotechnology and Stem Cell
Engineering. BERG activities have been developed and coordinated within research
laboratories. This structure allows researchers in each laboratory to focus on particular
research topics of Bioengineering, while exploring and strengthening cross-cutting
competences. The current structure features five laboratories:
Bioprocess Engineering and Biocatalysis Laboratory (BEBL)
Bioseparation Engineering Laboratory (BEL)
BioSystems Engineering Laboratory (BSEL)
Molecular Bioengineering Laboratory (MBL)
Stem Cell Bioengineering and Regenerative Medicine Laboratory
(SCBL)
Main Indicators
BERG was established in 1991 as one of the initial three research groups of the Centre for Biological and
Chemical Engineering at IST, under the coordination of Prof. Joaquim Sampaio Cabral. The research carried
out throughout the years has been considered of excellent level by the international committees, which regu-
larly evaluate the research units funded by the Portuguese Ministry of Education and Science. The main
output of the activities performed by BERG members in 2012 is summarized in the following tables.
Human Resources
In 2013, BERG has 102 researchers integrated into the five laboratories, of these 25 have a PhD degree, 43
a master degree, 33 a bachelor degree and 1 undergraduate.
Publications
In 2013, the output of BERG’s activities includes the publication of 38 scientific articles in peer-reviewed
journals, 3 patents, 2 book and 7 book chapters, among other publications, including conference proceed-
ings, invited oral communications, oral communications and poster presentations in distinct international and
national conferences.
Human Resources Number
Faculty 11
Research Scientists 5
Post-doctoral Fellows 9
PhD Students 32
Research Assistants 11
MSc Students 33
Technicians 1
Male
Female
PhD
MSc
BSc
Undergraduate
20 9 13 Annual Report
Main Indicators
Type of Event Name of Event Committee
Course Scientific and Organising Committee of the International Advanced Course on Regenerative Medicine Manufacturing, Tavira, Algarve, Portugal, April
Joaquim Cabral, Margarida Diogo, Cláudia da Silva
Conference Scientific Committee of International Conference on BioPartitioning and Purification “BPP”, New Port, USA, October Raquel Aires Barros
Conference Coordinating Committee of the joint 9th European Congress of Chemical Engineering (ECCE9) / 2nd European Conference of Applied Biotechnolo-gy (ECAB2)
Joaquim Cabral,
Conference Scientific Committee of the 8th International Meeting of the Portuguese Society for Stem Cells and Cell Therapies, University of Algarve, Faro
Joaquim Cabral, Cláudia da Silva, Margarida Diogo
Conference Scientific Committee of the Portuguese Congress of Microbiology and Biotechnology | Microbiotec’2013, Aveiro, Portugal, December
Joaquim Cabral, Miguel Pra-zeres, Raquel Aires-Barros
Workshop Scientific and Organising Committee, “5º curso teórico-prático de Cartila-gem Articular”, Lisbon, Portugal, November Joaquim Cabral
Working Group Regenerative Medicine Manufacturing of the European Society of Bio-chemical Engineering Science “ESBES” Joaquim Cabral
Working Group Scientific Committee of European Section on Applied Biocatalysis “ESAB” Joaquim Cabral, Luís Fonse-ca
Working Group Downstream Processing of the European Society of Biochemical Engineer-ing Science “ESBES” Raquel Aires-Barros
Working Group Scientific Board of TERMIS Thematic Group on "Bioreactor Technologies" Joaquim Cabral
Scientific events
In 2013, the members of BERG have participate in organizing and scientific committees of national and in-
ternational conferences, research networks, working groups and sections of the European Federation of
Biotechnology and of the Tissue Engineering and Regenerative Medicine International Society (TERMIS).
Type of Publication Number
Articles in international peer-reviewed journals 38
Articles in conference proceedings 2
Books 2
Book chapters 7
Patents 3
Invited oral communications in international conferences 8
Invited oral communications in national conferences 8
Oral communications in international conferences 13
Oral communications in national conferences 10
Poster communications in international conferences 26
Poster communications in national conferences 17
PhD Thesis 7
MSc Thesis 69
Research Activities
2013 BERG Annual Report
Biosystems Engineering Laboratory BSEL
Molecular Bioengineering Laboratory MBL
Stem Cell Bioengineering and
Regenerative Medicine Laboratory SCBL
Bioprocess Engineering and Biocatalysis
Laboratory BEBL
Bioseparation Engineering Laboratory BELL
Bioprocess Engineering and Biocatalysis
BEB
L
Objectives
The Bioprocess Engineering and Biocatalysis La-
boratory aims at developing competitive and sus-
tainable technologic platforms and analytical meth-
odologies and tools with high potential and econom-
ic impact. In the field of biocatalysis the main goal is
to design and produce value-added bioproducts by
bioconversion using enzymes and microbial cells
from micro- to pilot-scale in the field of White Bio-
technology, namely in key areas such as of food
and feed, aroma, pharmaceutical and fine chemistry
industries, and biofuels, as well as to improve bio-
catalyst performance. A second area is the develop-
ment of new analytical methodologies and devices
specially biosensors and microfluidic systems de-
signed for monitoring and control of bioprocesses,
environment, food and water and healthcare. The
current projects are focused on the development of
technological platforms for biocatalysis and analyti-
cal tools to link process and product design orga-
nized in four major areas: Biocatalysis and Biotrans-
formation, ii) Bioreaction Engineering and iii) Bio-
sensors and Miniaturization.
Research Topics
1. Biocatalysis and Biotransformations - Design and
thorough characterization of reaction media and
operational strategies aiming at the implementation
of robust, high conversion bioconversion systems.
These are anchored in enzymatic platforms, namely
cutinase, penicillin acylase, inulinase and invertase,
targeted for the production of esters (flavors, bio-
diesel, chiral compounds and glycerol and oil inter-
mediates for bioplastic production), antibiotic inter-
mediates and semi-synthetic antibiotics and sweet-
eners. New methodologies on the use of lipases in
miniemulsion systems have been used on the enzy-
matic resolution of secondary alcohols with eco-
nomical interest. Bio-degradable zwitterionic com-
pounds are being synthesized in order to be used
as drug delivery vehicle. Moreover, the work devel-
oped contributed with valuable insight towards the
definition of major guidelines for rational bioprocess
design and development. Whole cells of mesophilic
bacteria have been improved, by favouring adaptive
mechanisms, to increase biocatalytic yields and
allow bioremediation processes under extreme con-
ditions of temperature and pH and in the presence
of high concentrations of salt and copper.
2. Bioreaction Engineering - Efficient and competi-
tive bioconversion systems aimed either at the pro-
duction of oligosaccharide syrups or at the hydroly-
sis of lignocellulosic waste, were developed. The
core of such systems relied on polyvinyl alcohol
based materials as enzyme carriers. Enzymatic (viz.
lipase, cutinase) and whole cell platforms (yeast
strains) are being used within the scope of an inno-
vative approach for the sustainable production of
biodiesel and jet biofuel. Further research efforts
are being made towards the production of jet-fuel
within the scope of microbial cell factories. Oxido-
reductases are used in combination with an innova-
tive material, Ion Jelly, for structuring enzymatic
biofuel cells. Zwitterionic compounds and fibers are
being synthesized as new electrolytes for the use
on the fabrication of thin film batteries based on Ion
Jelly technology. Rhodococcus cells are being as a
source of specialized fatty acids for biofuel produc-
tion and as a model bacterium to study biocatalyst
adaptation to reaction conditions. Pseudozyma spp
are being used for production of mannosylerythritol
lipids (MEL), a glycolipid/biosurfactant, for the first
time, from lignocellulosic materials.
3. Biosensors and Miniaturization - Nano/micro-
biocatalysts (biocomposites) are being developed
based on hydrogels, sol-gel, protein/cell assemblies
and magnetic nano-particles. New biomaterials
compatible with enzymes and other bio molecules
are being used as matrixes on the development of
biosensors. Miniaturized platforms, namely minia-
ture, meso- and microreactors, of either microstruc-
tured and non-microstructured nature are used for
bioprocess intensification. Reliable scaling strate-
gies, from those platforms to, at least bench-scale,
has been looked into. The design and assembly of
microreactors using low-cost, easily available mate-
rials and simple methodologies was performed and
the proof-of-concept was validated, using model
systems based on inulinase and invertase hydrolytic
activities. A multidisciplinary approach, from surface
characterization to hydrodynamics and catalytic
behavior, is being implemented for a thorough char-
acterization of enzymatic microreactors. High
throughput systems were also used to test the abil-
ity of essential oils from aromatic Mediterranean
plants to prevent biofilm formation and to study cel-
Luís Fonseca (PI), Carla Carvalho, Pedro Fernandes, Frederico Ferreira
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lular adaptation mechanisms to different toxic com-
pounds. A method involving bacterial cells was
used as a non-destructive technique to detect micro
defects in microfabrication components.
Main Achievements
It was shown, for the first time that polyunsatu-
rated fatty acids (PUFA) are synthesized during
short-time responses of Rhodococcus to osmot-
ic stress. PUFA were thought to be only pro-
duced solely by marine bacteria.The under-
standing of bacterial adaptation mechanisms
was used to improve polyhydroxyalkanoate pro-
duction
Aresilient system for cellobiose hydrolysis an-
chored in β-glucosidase entrapped in polyvinyl
alcohol hydrogels was successfully implement-
ed.
Design and implementation of efficient, low-cost
flow enzyme microreactors, allowing for the con-
tinuous production of fructose syrup from inulin.
Microscopic analysis of the microreactors pro-
vided a better understanding of enzyme behav-
ior.
Development of a process for sustainable pro-
duction of mannosylerythritol lipids (MEL), a gly-
colipid/biosurfactant with potential industrial ap-
plication, from lignocellulosic materials was de-
veloped and patented exploiting the natural fea-
tures of Pseudozyma spp. (work performed in
collaboration with LNEG).
Economical and environmental assessment of
different processes for active pharmaceutical
ingredients degenotoxification combining experi-
mental and theoretical studies (work performed
in collaboration with Hovione FarmaCiencia SA).
Zwitterionic compounds and fibers are being
synthesized as new electrolytes for the use on
the fabrication of thin film batteries based on Ion
Jelly technology.
Enzymatic platforms in miniemulsion systems,
namely cutinase were targeted for the produc-
tion of esters as fruity flavors and hydrolysis of
oil used as intermediates for bioplastic produc-
tion and resolution of secondary alcohols with
economical interest.
New biomaterials compatible with enzymes and
other bio molecules are being used as matrixes
on the development of biosensors.
Selected Publications
Székely, G., Bandarra, J., Heggie, W., Ferreira,
F.C., Green Chem. 15 (2013) 210
Figueira, J.A., Sato, H.H., Fernandes, P., J. Agric.
Food Chem., 61 (2013) 626-634
Ribeiro, E.M., Fernandes, P., Current Biotechnol., 2
(2013) 47-52
de Carvalho, R.N.L., Lourenço, N.M.T., Gomes,
P.M.V., da Fonseca, L.J.P., J. Polym. Sci., Part B:
Polym. Phys., 51 (2013) 817-825
Lopes, J.M., Paninho, A.B., Molho, M.F., Nunes,
A.V.M., Rocha, A., Lourenco, N.M.T., Najdanovic-
Visak, V., J. Chem. Thermodyn., 67 (2013) 99-105.
Bioseparation Engineering BEL
Objectives
The Bioseparation Engineering Laboratory aims at
the design and development of novel purification
processes in order to intensify and optimize the
downstream processing of proteins and biopharma-
ceuticals, with special emphasis on monoclonal
antibodies (mAbs), virus and VLPs. Several alterna-
tives to the currently established downstream pro-
cessing platforms of recombinant proteins and bio-
nanoparticles are being explored, with main focus
on aqueous two-phase extraction, nano-magnetic
separation and monolithic chromatography, from a
nano-scale to industrial scale. Additionally, tailor-
made synthetic ligands are being used aiming to
improve protein purification.
Research Topics
1. Aqueous two-phase systems (ATPS) for biophar-
maceuticals purification – The overall goal of this
contribution is to design an innovative downstream
process based on ATPS, for the purification of high-
value biomolecules from complex media, compris-
ing cell separation and bioproduct selective extrac-
tion, envisaging process integration and intensifica-
tion. This extraction-based technology is applied to
mAbs, pDNA, VLPs, cellular bodies, and intracellu-
lar or secreted proteins. In the case of proteins lo-
cated in the intracellular space, ATPS are dove-
tailed with electroextraction to increase the selectivi-
ty of the whole processing scheme. Efficient models
are being developed in order to predict protein parti-
tion in ATPS, contributing for a better understanding
of the mechanisms responsible for partitioning of
biomolecules and the parameters governing parti-
tion.
2. Bio-inspired affinity nanoparticles for antibody
recognition – Novel biomimetic affinity nanoparti-
cles, based on the conjugation of a Protein L-mimic
affinity ligand with thermosensitive amino-
functionalised PNIPAM microgels, have been de-
signed and synthesised. Adsorption screening with
three different model-proteins (bovine serum albu-
min, a commercial monoclonal antibody (mouse
IgG1 isotype) and human IgG) demonstrated that
such bio-inspired nanoparticles are able to selec-
tively recognize and capture antibody molecules in
both pure and impure/complex media.
3. Nano-magnetic separation of biopharmaceuticals
– The main focus is on the development of magnet-
ic nanoparticles (MNPs) suitable for the purification
of mAbs envisaging process integration and imple-
mentation of high scale magnetic separators. Func-
tionalized magnetic particles, based on boronic ac-
id, with high capacities for the therapeutic targets
are being applied in high gradient magnetic separa-
tion (HGMS) units or combined with ATPS. Associa-
tion of ATPS with affinity MNPs can improve the
throughput of the process but also the selectivity of
the separation. Process integration is evaluated by
using unclarified extracts of mAbs directly in HGMS
or combined with ATPS.
4. Alternative chromatographic ligands for antibody
purification – Novel affinity and mixed-mode ligands
are being designed and developed for the purifica-
tion of mAbs. Particular focus is being given to phe-
nyl boronate derivatives, which have been shown to
interact in a specific way with antibodies. The immo-
bilization of these ligands on to the surface of su-
pramacroporous monoliths (cryogels) is also being
addressed as a tool to integrate both clarification
and capture in just one step, and thus to capture
mAbs directly from cell culture media without any
cell removal step upstream. Removal of residual
DNA, host cell proteins and aggregates is being
evaluated using membrane adsorbers functional-
ized with anion-exchanger and hydrophobic ligands.
5. High throughput bioseparation platforms – De-
sign of an automated high-throughput microfluidic
Lab-on-Chip (LOC) platform based on ATPS allow-
ing process integration, optimization, and analysis is
being performed. The ATPS microfluidic platform is
being applied to mAbs extraction as an effective
tool to accelerate bioprocess design and optimiza-
tion and to integrate cell separation with mAbs puri-
fication and detection. Using the same concept, a
prototype microfluidic Lab-on-Chip platform for the
detection of contaminants in food products integrat-
ing sample preparation and toxin detection is also
being developed.
M. Raquel Aires-Barros (PI), Ana Azevedo, M. Ângela Taipa
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Main achievements
It was demonstrated that aqueous two-phase
extraction (ATPE) process can be used as a
platform for the capture of antibodies, overcom-
ing some of the limitations encountered using
the typical chromatographic processes, besides
inherent advantages of scalability, process inte-
gration, capability of continuous operation, and
economic feasibility. A continuous ATPE pro-
cess based on a PEG/phosphate system was
developed for the capture of human immuno-
globulin G and successfully applied to a Chinese
hamster ovary and a PER.C6 cell supernatant.
Prediction of partition coefficient of eight ionized
compounds was achieved in different ATPS by
the multiple linear regression analysis using the
linear solvation energy relationship (LSER)
equation.
Affinity magnetic separation prooved to be a
versatile separation process for antibodies purifi-
cation and an alternative to Protein A chroma-
tography, considering the fast process, gentle
conditions, potentially high binding capacities
and lower cost of the ligands employed.
PNIPAM-based nanoparticles were conjugated
with a protein L mimetic ligand and used to bind
selectively to IgG molecules.
Stimuli-responsive magnetic nanoparticles were
successfully prepared by a miniemulsion
polymerization method and used to purify a
monoclonal antibody from a CHO cell culture
supernatant, allowing a removal of more than
98% of HCP.
Selected Publications
Rosa, P.A.J., Azevedo, A.M., Sommerfeld, S., Mut-
ter, M., Baecker, W., Aires-Barros, M.R., Biotech-
nol. J., 8 (2013) 352-362
Madeira, P.P., Bessa, A., Alvares-Ribeiro, L., Aires-
Barros, M.R., Rodrigues, A.E., Zaslavsky, B.Y., J.
Chromatogr. A, 1274 (2013).82-86
Borlido, L., Azevedo, A.M., Roque, A.C.A., Aires-
Barros, M.R., Biotechnol. Adv., 31 (2013) 1374-
1385
Silva, C.S.O., Lansalot, M., Garcia, J.Q., Taipa,
M.A., Martinho, J.M.G., Colloids Surf. B, 112 (2013)
264-271
Borlido, L., Moura, L., Azevedo, A.M., Roque,
A.C.A., Aires-Barros, M.R., Farinha, J.P.S., Biotech-
nol. J.,8 (2013) 709-717.
BioSystems Engineering
BSEL
Objectives
To link process and product throughout design, de-
velopment and biomanufacturing, systems engi-
neering approaches must be used or developed
anew. Process analytical technology (PAT) repre-
sents the combined use of different tools applicable
through many of those stages. Though PAT is still
mostly process centred, it can be used within the
QbD (quality by design) context to link process to
product. The main research topics at BSEL
(BioSystems Engineering Lab) are focused on: i)
work with new or established PAT tools, ii) whole
process/product design and analysis (cell-process-
product), iii) systems engineering applied to modern
manufacturing, and iv) pharmaceutical engineering.
Research Topics
1. Process Analytical Technology Tools – PAT in-
volves the application of process analytical chemis-
try (i.e., in-process monitoring techniques and
chemometrics), multivariate data analysis (MVDA;
e.g., data-based modelling techniques), and pro-
cess control techniques (namely, use of process
data with multivariate supervision and diagnosis
strategies). All these activities are done with the aim
of characterizing the state of a system at any given
time real-time and to be used in process optimiza-
tion and control. The perspective taken in PAT is
that of the process (not the sample or that of a sin-
gle parameter over time). In this research topic the
use of spectroscopy techniques specially suited for
industrial applications is explored in diverse con-
texts (pharma/biopharma) and within the overall
PAT context and aims.
2. Whole Process/Product Design and Analysis –
Systems biology and ‘omic’ approaches have pro-
vided a general physiological and metabolic engi-
neering understanding of several important microor-
ganisms, while bioprocess systems engineering has
benefited from the integration of monitoring, model-
ling, control and optimization. In this topic the links
within and between USP (up-stream processing:
biotransformation) and DSP (down-stream pro-
cessing: bioseparation) are explored at the three
levels of cell-process-product. Concepts such as
process and product design spaces and all aspects
related to quality-by-design are examined for phar-
ma and biopharma processing.
3. Systems Engineering Applied to Manufacturing –
While product innovation has been the key issue in
pharma and biopharma in the past, manufacturing
has remained relatively static (e.g., locked-validated
processes). Continuous improvement and opera-
tional excellence practices are entering pharma/
biopharma manufacturing and transforming these
industries as happened elsewhere decades ago. In
this research track, science and technology driven
manufacturing paradigms are the main topics exam-
ined, as the way forward to achieve operational ex-
cellence and sustainability throughout process/
product life-cycle. Adapting tools and metrics from
the disciplines of operation excellence in other in-
dustries to biomanufacturing, is the main focus on
this topic.
4. Pharmaceutical Engineering – New paradigms in
design and manufacturing of small and large thera-
peutically active (API) molecules and drug products
(formulated APIs), include continuous microreaction
technologies (MRT). It is relatively straightforward
to scale-down and operate in continuous mode
some API chemical synthesis reactions in micro-
reactors. It is still very complex or yet unfeasible to
operate in continuous mode most unit operations
involving suspended solids (e.g., crystallization),
biotransformations and some bioseparations. In
this research topic work with off-the-shelf MRTs is
being initiated to examine both feasibility and opera-
bility issues of plant miniaturization and process
intensification of small API molecules manufactur-
ing. As experience and knowledge are established
more complex types of products and unit operations
will be examined.
José Menezes (PI)
20 17 13 Annual Report
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Main Achievements
New PhD students admitted to work on new
aspects of QbD on drug-substance (API) and
formulated drug-products (2013 – 2016):
Alexandra Hertrampf, Risk Mitigation for
Pharmaceutical Raw-Materials and Prod-
ucts, Using Quality by Design Techniques.
Supervised by Prof. J.C. Menezes and
Merck-Millipore (Germany) Dr J.Schewitz.
Lúcia V. Sousa, Establishing QbD Principles
to Development and Lifecycle Managment
of Analytical Methods in Pharmaceutical
Quality Control. Supervised by Prof. J.C.
Menezes and Hovione (Portugal) Dr A. Ra-
mos.
Establishing an institutional cooperation with
Brazil’s top University (USP in Sao Paulo) to
establish a research and masters program in
Pharmaceutical Engineering at the Faculty of
Pharmacy, USP and to enable PhD and MSc
student exchange with IST (UL)
Presidential Award of Merit for Excellence in
Academia-Industry Collaborations – COTEC
2013
Selected Publications
Hakemeyer, C., Strauss, U., Werz, S., Folque, F.,
Menezes, J.C., J. Biotechnol., 8 (2013) 835-846
Vicente J, Pinto J, Menezes JC, Gaspar F., Powder
Technol., 247 (2013) 1-7
Menezes JC, The PAT Toolbox & Skills-Set. 9th.
Kolloquium Prozessanalytik – 100 Years of PAT,
BASF-Ludwigshafen – Nov. 28-29, 2013. (Keynote
Invited Speaker)
Menezes JC. A Critical Discussion of EMA's NIR
Draft Guideline on the use of NIRS by the Pharma-
ceutical Industry. IFPAC-2013, Jan. 22-25, 2013,
Baltimore (MD), USA. (Invited Talk)
MB
L
Molecular Bioengineering
Objectives
The Molecular Bioengineering Laboratory is dedi-
cated to the tailored modification of nucleic acids,
proteins and cells with the goal of creating useful
products and designing more efficient processes for
the industrial and health biotechnology areas. This
activity involves the convergence of research areas
such as molecular biology, microbiology, biochemis-
try and immunology. Three major research pro-
grams are pursued: i) plasmid vectors, ii) bio-
recognition and bio-interfacing and iii) microbial cell
factories. In the case of plasmid vectors, the goal is
to address the scientific/technological challenges
associated with the emergence of plasmid biophar-
maceuticals. In the bio-recognition and bio-
interfacing topic, the goal is to develop (bio)
molecular constructs to anchor biomolecules to sur-
faces, nano/microstructured biomimetic surfaces for
controlled cell adhesion, adsorption materials for
biomolecule purification and platforms for the ma-
nipulation/detection of DNA, proteins and cells at
the micro-scale. The goal of the microbial cell facto-
ries topic is to engineer microbial cells to improve
the production of specific biomolecules.
Research Topics
The following research topics are pursued within
each research line:
i) Plasmid vectors
1. Plasmid design for improved stability, delivery
and manufacturing. Vectors are designed to im-
prove the manufacturing of plasmids and minicircles
used for DNA vaccination, gene therapy and protein
production by transient transfection. Marine organ-
isms are screened for drugs that inhibit nucleases,
stabilise plasmids and increase transfection activity.
Delivery systems (electroporation, liposomes, car-
bon tubes, polymeric microparticles) are developed
to increase DNA uptake and transcription levels.
2. DNA vaccines and gene therapy. DNA vaccine
candidates are constructed by cloning antigenic
proteins associated with sleeping sickness/avian flu
and tested in animal models for their ability to gen-
erate cellular and humoral responses, and to pro-
vide immunisation. The possibility of using plasmids
to deliver the cytotoxic bacterial protein azurin to
cancer cell models is under evaluation
(collaboration with BSRG).
ii) Bio-recognition and bio-interfacing
1. Biomimetic ligands and surfaces. Synthetic pro-
tein-mimic affinity ligands are designed, synthe-
sized, screened and used to anchor, stabilise and
purify proteins, oligonucleotides and plasmid DNA.
Natural surface structures are transferred onto tech-
nical materials using replica moulding techniques
and characterized in terms of their nano/
microstructure, hydrophobicity, self-cleaning proper-
ties and ability to prevent/promote cell adhesion.
2. Adsorption materials. Chromatographic mem-
branes and supports are modified with specific lig-
ands to improve the purification of biomolecules
(plasmids, antibodies). Covalent immobilization of
biomolecules and assembling of molecular probes
on AFM cantilevers is pursued to characterize bind-
ing interactions with these adsorptive materials.
3. CBM-based fusions for bioactive paper applica-
tions. Carbohydrate Binding Modules (CBMs) are
screened, characterized, fused with specific pro-
teins (e.g. ZZ fragments, enzymes), produced and
used to functionalize cellulosic materials with the
goal of developing sensors for molecular diagnos-
tics, enzyme-based analytical test strips and spe-
cialised filters.
4. Platforms for the handling of DNA, proteins and
cells at the micron scale. Thin film technologies,
chemical modification, microfluidics, photodetectors
and photoreflectors are used to develop microchip
platforms for the colorimetric, chemiluminescent
and fluorescent detection of biorecognition events
like DNA hybridization, antigen-antibody interac-
tions, metabolic cell activity and receptor (GPCR)
binding.
iii) Microbial cell factories
1. Engineering of E. coli and Lactic Acid Bacteria
(LAB) strains. E. coli and LAB strains are engi-
neered to produce high amounts of biomolecules
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(plasmid DNA, curcumin (LAB strains) and pro-
teins) by mutating key genes on the glycolytic path-
way. The impact of the new strains on the down-
stream processing and overall quality and biological
activity of biomolecules is studied.
Main Achievements
A new pDNA production strain (GALG20) was
created by knocking out the pgi gene in E. coli,
which produces 25-fold more pDNA than the
parental strain.
The impact of quality attributes (impurity con-
tent, plasmid charge) of pDNA isolated with dif-
ferent purification methods on the characteris-
tics of lipoplexes prepared thereof (size, zeta
potential, stability) and on their ability to trans-
fect mammalian cells was demonstrated.
A hydrophobic interaction membrane chroma-
tography step which relies on phenyl membrane
adsorbers and a stepwise elution strategy was
integrated in a pDNA production process.
Protein stabilization was achieved by a novel
approach based on the adsorption and estab-
lishment of affinity-like interactions with a biomi-
metic triazine-scaffolded ligand.
An integrated analytical system that conjugates
an indirect competitive enzyme-linked immuno-
sorbent assay strategy developed in PDMS mi-
crofluidics with integrated microfabricated hy-
drogenated amorphous silicon was successfully
used for the determination of ochratoxin A.
Microfluidic channels with patterned electrodes
were developed to trap E. coli cells by dielectro-
phoresis in stagnant and in-flow fluidic situa-
tions.
A highthroughput methodology was developed
to characterize the binding of carbohydrate
binding module (CBM) to cellulose supports.
Selected Publications
Gonçalves, G.A.L., Prazeres, D.M.F., Monteiro,
G.A., Prather, K.L.J., App. Microbiol. Biotechnol.,
97 (2013) 611-620
De la Vega, J., Braak, B., Monteiro, G.A., Azzoni,
A.R., Prazeres, D.M.F., J. Pharm. Sci. 102 (2013)
3932-3941
Raiado, L.P., Prazeres, D.M.F., Mateus, M., J.
Chromatogr. A, 1315 (2013) 145-151
Sousa, I.T., Lourenço, N.M.T., Afonso, C.A.M., Tai-
pa, M.A., J. Mol. Recognit., 26 (2013) 104-112
Novo, P., Moulas, G., Prazeres, D.M.F., Chu, V.,
Conde, J.P., Sensors Act. B: Chemical 176 (2013)
232-240
Donato, S.S., Chu, V., Prazeres, D.M.F., Conde,
J.P., Electrophoresis 34 (2013) 575-582.
SCB
L
Stem Cell Bioengineering and
Regenerative Medicine Laboratory
Objectives
The Stem Cell Bioengineering and Regenerative
Medicine Laboratory aims at developing controlled
bioreactor systems for the ex-vivo expansion of
stem cells and their controlled differentiation into
specific cell types, as well as their integration with
advanced bioseparation in order to purify Stem
Cells/progenitors and their derivatives targeting
their application in Regenerative Medicine settings
and toxicology/pharmacological testing. As stem
cells (SC) are rare, their isolation and expansion/
differentiation in vitro significantly increases the
cell population available for Cellular and Gene
Therapy, Tissue Engineering, high-throughput drug
screening and pharmacological toxicity testing and
stem cell research. Human hematopoietic stem/
progenitor cells (HSC), human mesenchymal stem/
stromal cells (MSC), as well as human and mouse
pluripotent stem cells (both embryonic (ESC) and
induced pluripotent stem cells (iPSC)) and neural
stem cells (NSC) are used as model systems. Four
main research topics are being pursued:
Research Topics
1. Clinical Manufacturing of SC-based Therapies
Our focus is the manufacturing of clinical-grade
Stem/Progenitor Cells (S/PC) to be used as
ATMPs for first-in-human studies in collaboration
with our clinical partners, specifically human Mes-
enchymal Stem Cells (MSC) for Acute Myocardial
Infarction treatment and Umbilical Cord Blood
Hematopoietic Stem/Progenitor Cells expanded in
co-culture with MSC to be infused in hemato-
oncological patients. The main goal is to optimize
our previously microcarrier-based platform for
MSC cultivation and its GMP implementation. A
systematic analysis of S/PC is being pursued
through culture parameters (shear, oxygen) control
and their impact on cell product potency
(immunomodulation, trophic activity, differentiation
ability). Specifically we aim to set-up a quality con-
trol platform by identifying reliable potency bi-
omarkers to assure safe and clinically effective
expanded cells. We propose to generate pre-
clinical data for the development of both ATMPs
and dosages to be tested will be determined based
on potency levels, according to EMA/INFARMED.
2. Multi-Scale Strategies for Human Pluripotent
Stem Cell Bioprocessing
The main objective is to develop Integrated Biopro-
cesses to overcome the main technological barri-
ers that presently limits the application of human
Pluripotent Stem Cells (PSC), embryonic (ESC)
and induced PSC (iPSC), and their derivatives.
Large-scale production of PSC-derived neural pre-
cursors and cardiomyocytes has been addressed
to leverage the emergence of alternative therapies
and screening tools for neurodegenerative and
cardiovascular diseases. Bioreactors will be used
to integrate PSC expansion and differentiation
based on tightly-controlled microenvironments us-
ing tailor-made niche-inspired microcarriers. Micro-
environments will be designed based on HTS stud-
ies on the effect of niche parameters. Modelling
will be used to uncover complex interactions be-
tween different niche components and systems
biology approaches will be applied for better un-
derstanding of pluripotency at the molecular level.
Affinity-based separation methods will be integrat-
ed with bioreactors for purification of PSC deriva-
tives, including the depletion of tumorigenic PSC.
In particular, monolithic matrices functionalized
with cost-effective and highly-selective ligands
(e.g. aptamers) will be used.
3. Ex-vivo Gene Therapy for Regenerative Medi-
cine Applications
Novel gene carriers (minicircles) will be tested into
SC/progenitors to prolong gene expression and
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augment cell survival while guaranteeing extremely
low probability of genome integration. The main
focus is the development of Gene Activated Matri-
ces, composed by hydrogels embedding minicir-
cles, encoding genes involved in specific differenti-
ation fates. With this approach, these genes are
released in a sustained mode into SC/progenitors
and expressed at low levels assuring the formation
of native-like tissue and/or able to promote endog-
enous repair in vivo. By using human MSC our
main goal is to promote cartilage regeneration and
angiogenesis in ischemic heart for cardiac regen-
eration.
4. Tailoring biomaterials to support stem cell culti-
vation
The aim is to mimic the natural features of extra-
cellular matrix to promote cell-cell and cell-material
interactions and cellular adhesion, as well as to
add artificial functions facilitating cell processing.
The envisaged KET include i) Electrospun aligned
nanofiber scaffolds and scalable plate&frame bio-
reactors, to direct cell organization and function
targeting neural or cardiac regeneration ii) Encap-
sulation/hydrogel-based systems that will be tai-
lored for chondrogenesis, iii) Microcarriers for SC/
progenitors cultivation, and iv) stimulus-responsive
materials (e.g. glucose, temperature) facilitating
cell harvesting or controlled delivery of small mole-
cules and bio-macromolecules (genes and pro-
teins).
Main Achievements
Towards the definition of the pros and cons of
an allogeneic versus autologous MSC-based
therapy for acute myocardial infarction (AMI),
we performed a comparative study of the
proliferative, differentiative, immunomodulato-
ry and trophic potential of bone marrow (BM)-
derived MSC obtained from healthy donors
and AMI patients in collaboration with Depart-
ment of Cardiology, Hospital Santa Marta
(HSM), Lisboa. Also together with HSM, and
Faculdade de Medicina Veterinária, we suc-
cessfully implemented a pre-clinical in vivo
model for AMI – the swine. This model al-
lowed us to generate first pre-clinical data on
the safety of the intra-coronary (IC) admin-
istration of BM MSC, demonstrating definitive
evidence of microcirculatory disruption upon
IC MSC infusion in a large animal model
closely resembling human cardiac physiology,
function, and anatomy.
The scalable xeno-free microcarrier-based
reactor system previously established at
SCBL-RM for the production of MSC from
different human sources was successfully
optimized with the final aim of increasing
overall cell productivity. Initial cell adhesion to
the beads was maximized by establishing an
optimized protocol of cell seeding under inter-
mittent agitation and by using ready-to-use
xeno-free plastic microcarriers without the
need of a pre-coating step.
In collaboration with the Department of Urolo-
gy - Hospital Garcia de Orta and Wake Forest
Institute for Regenerative Medicine (WFIRM),
we successfully established a method for the
effective decellularization of animal urethra/
rhabdosphincter tissue towards the establish-
ment of a suitable scaffold as a basis of a
urological tissue engineering strategy specifi-
cally targeting the screening and development
of novel potential drugs and therapies for
Stress Urinary Incontinence.
A robust culture platform was established for
the expansion, neural commitment and neu-
ronal differentiation of hiPSC using serum-
free chemically-defined media and a xeno-
free culture substrate. Importantly, this culture
platform was successfully integrated with the
affinity-based purification of hiPSC-derived
neural precursors paving the way towards the
development of an integrated bioprocess for
the large-scale production and purification of
hiPSC-derived neurons that may be potential-
ly used for drug screening and disease mod-
elling and ultimately for Regenerative Medi-
cine applications. This culture platform is
presently being used for the robust production
of mature patient-specific neuronal cells from
hiPSC for disease modelling of Rett Syn-
drome, in collaboration with IMM.
In parallel, a robust culture platform has also
been established and optimized for differenti-
ation of model hiPSC lines into cardiomyo-
cytes under static conditions, using an adher-
ent monolayer culture system, and based on
the use of small molecules and a chemically-
defined culture medium.
The scalable microcarrier-based culture plat-
form previously developed for expansion of
hiPSC in spinner flasks has been adapted to
the new generation xeno-free E8 culture me-
dium and using xeno-free microcarriers.
A 3D microarray platform has been developed
in collaboration with Professor Jonathan
Dordick, at the Rensselaer Polytechnic Insti-
tute (RPI/USA), to perform high-throughput
studies of human Neural Stem Cell (hNSC)
Differentiation and Toxicology. By using this
platform it was possible to screen for the dif-
ferential toxicity of small molecules to hNSCs
which may help to predict, in vitro, which com-
pounds pose an increased threat to neural
development and should therefore be priori-
tized for further screening and evaluation.
Neural stem cells were successfully transfect-
ed with minicircles showing higher expression
of the gene of interest and higher cell viabili-
ties when compared with cells transfected
with the respective plasmid DNA.
Assessment of the effect of different layer-by-
layer extruded scaffolds configurations in cell
behaviour on human BM MSC expansion and
differentiation towards chondrocytes, showing
an higher impact in higher chondrocyte popu-
lation is obtained when expansion takes place
under hypoxia (5% O2) and that cell distribu-
tion and dimension of chondrocyte aggre-
gates depend strongly on fiber alignment
(work performed in collaboration with CDRsp,
Polytechnic Institute of Leiria, Portugal).
Selected Publications
Fernandes, T.G., Diogo, M.M., and Cabral, J.M.S.,
"Stem Cell Bioprocessing: For Cellular Therapy,
Diagnostics and Drug Development", Woodhead
Publishing Series in Biomedicine No. 40, Wood-
head Publishing, Cambridge (ISBN: 978-1-907568-
88-6)
20 23 13 Annual Report
Madeira, C., Rodrigues, C.A.V., Reis, M.S.C., Fer-
reira, F.F.C.G., Correia, R.E. S. M., Diogo, M.M.,
Cabral, J.M.S., Biomacromolecules, 14 (2013)
1379-1387
Oliveira, P.H., Boura, J.S., Abecasis, M.M., Gim-
ble, J.M., da Silva, C.L., Cabral, J.M.S., Stem Cell
Res., 9 (2013) 225-236
dos Santos, F., Andrade, P.Z., da Silva, C.L., Ca-
bral, J.M.S., Biotechnol. J.,8 (2013) 644-654
Simões, I.N., Boura, J.S., dos Santos, F., Andrade,
P.Z., Cardoso, C.M.P., Gimble, J.M., da Silva,
C.L., Cabral, J.M.S., Biotechnol. J., 8 (2013) 448-
58.
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Research Team
2013 BERG Annual Report
Full Professors
Associate Professors
Assistant Professors
Research Scientists
Joaquim M.S. Cabral Ph.D. Instituto Superior Técnico, 1982 Full Professor Phone: +351-218419063 e-mail: [email protected]
Research Areas and Interests
Stem Cells Research for Tissue Engineering and Regenerative Medicine; Stem Cell Bioprocessing and
Manufacturing: development of novel stem cell bioreactors and advanced bioseparation and purification
processes.
Recent Selected Publications
T.G. Fernandes, M.M. Diogo and J.M.S. Cabral, “Stem Cell Bioprocessing: For cellular therapy, diagnos-
tics and drug development”, Woodhead Publishing Series in Biomedicine No. 40, UK, pp. 250 (2013)
C.A.V. Rodrigues, T.G. Fernandes, M.M., Diogo, C.L. da Silva, J.M.S. Cabral “Bioreactors for Stem Cell
Expansion and Differentiation”, in Stem Cell Engineering: Principles and Practices, Schaffer, D., Bronzino,
J.D., Peterson, D.R (eds), CRC Press, 10.1-10.28 (2013)
F.F. dos Santos, P.Z. Andrade, C.L. da Silva, J.M.S. Cabral, JMS “Bioreactor design for clinical-grade ex-
pansion of stem cells” Biotechnol. J. 8 (6) 644-654 (2013)
I.N. Simoes, J.S. Boura, F.F. dos Santos, C.L. da Silva, J.M.S. Cabral, “Human mesenchymal stem cells
from the umbilical cord matrix: Successful isolation and ex vivo expansion using serum-/xeno-free culture
media” Biotechnol. J. 8 (4) 448-458 (2013)
C. Madeira, C.A.V. Rodrigues, M.S.C. Reis, F.C.G. Ferreira, R.E.S.M. Correia, M.M. Diogo, J.M.S. Cabral
"Non-viral gene delivery to neural stem cells with minicircles by microporation", Biomacromolecules 14 (5)
1379-1387 (2013)
F. Gracio, J.M.S. Cabral, B. Tidor “Modeling Stem Cell Induction Processes” PLoS One 8 (5), DOI:
10.1371/journal.pone.0060240, ISSN: 1932-6203 (2013)
20 27 13 Annual Report
Research Areas and Interests
Responsible for the Bioprocess Engineering Laboratory (BEL) of the Bioengineering Research Group
(BERG) of Centre for Biological and Chemical Engineering, leader research unit of the Associate Labora-
tory Institute for Biotechnology and Bioengineering (IBB). Current research interests include bioseparation
of antibodies and cells through aqueous two-phase systems, magnetic nano-particles and chromatog-
raphy, and application of lab-on-a-chip microfluidic devices to biopharmaceuticals separation and process
integration, and biomolecules concentration.
Recent Selected Publications
Rosa, P.A.J., Azevedo, A.M., Sommerfeld, S., Mutter, M., Baecker, W., Aires-Barros, M.R., “Continuous
purification of antibodies from cell culture supernatant with aqueous two-phase systems: From concept to
process”, Biotechnol. J., 8(3), 352-362 (2013)
Borlido, L., Moura, L., Azevedo, A.M., Roque, A.C.A., Aires-Barros, M.R., Farinha, J.P.S., “Stimuli-
Responsive magnetic nanoparticles for monoclonal antibody purification”, Biotechnol. J., 8(6), 709-717
(2013)
Borlido, L., Azevedo, A.M., Roque, A.C.A., Aires-Barros, M.R., “Magnetic separations in biotechnology”,
Biotechnol. Adv., 31(8), 1374-1385 (2013)
Dsouza, R.N., Azevedo, A.M., Aires-Barros, M.R., Krajnc, N.L., Kramberger, P., Carbajal, M.L., Grasselli,
M., Meyer, R., Fernández-Lahore, M., “Emerging Technologies for the Integration and the Intensification of
Bioprocesses”, Pharm. Bioprocess., 1, 423-440 (2013)
Madeira, P.P., Bessa, A., Alvares-Ribeiro, L., Aires-Barros, M.R., Rodrigues, A.E., Zaslavsky, B.Y.,
“Analysis of amino acid-water interactions by partitioning in aqueous two-phase systems. I-Amino acids
with non-polar side-chains”, J. Chromatogr. A, 1274, 82-86 (2013)
Raquel Aires-Barros
Ph.D. Instituto Superior Técnico, 1990 Full Professor
Phone: +351-218419134 e-mail: [email protected]
Miguel Prazeres Ph.D. Instituto Superior Técnico, 1993 Associate Professor with Habilitation Phone: +351-218419133 e-mail: [email protected]
Research Areas and Interests
Responsible for the Molecular Bioengineering Lab of the Bioengineering Research Group at IBB-Institute
for Biotechnology and Bioengineering. Current research interests include nucleic acid engineering
(development of plasmid biopharmaceuticals and diagnostics), nanobiotechnology (lab-on-a-chip microflu-
idic devices with integrated biosensors using cells, proteins, and nucleic acids), bioactive paper applica-
tions and biomimetic surfaces, ligands and materials.
Recent Selected Publications
P. Novo, G. Moulas, D.M.F. Prazeres, V. Chu, J. P. Conde, “Detection of ochratoxin A in wine and beer
by chemiluminescence-based ELISA in microfluidics with integrated photodiodes”, Sens. Actuators B 176,
232-240 (2013)
S.S. Donato, V. Chu, D.M.F. Prazeres, J.P. Conde, “Metabolic viability of E.coli trapped by dielectrophore-
sis in microfluidics”, Electrophoresis 34, 575-582 (2013)
D.C. Martins, V. Chu, D.M.F. Prazeres, J.P. Conde, “Streaming currents in microfluidics with integrated
polarizable electrodes”, Microfluid. Nanofluid. 15, 361-376 (2013)
G.A.L. Gonçalves, D.M.F. Prazeres, G.A. Monteiro, K.L.J. Prather, “De novo creation of MG1655-derived
Escherichia coli strains specifically designed for plasmid DNA production”, App. Microbiol. Biotechnol. 97
611-620 (2013)
J. De la Vega, B. Braak, G.A. Monteiro, A.R. Azzoni, D.M.F. Prazeres, “Impact of plasmid quality on lipo-
plex-mediated transfection”, J. Pharm. Sci. 102, 3932-3941 (2013)
L.P. Raiado, D.M.F. Prazeres, M. Mateus, “Impact of plasmid size on the purification of model plasmid
DNA vaccines by phenyl membrane adsorbers”, J. Chromatog. A, 1315, 145-151 (2013)
S.A. Martins, G. Moulas, J.R. Trabuco, G.A. Monteiro, V. Chu, J.P. Conde, D.M.F. Prazeres, “Monitoring
intracellular calcium in response to GPCR activation using thin-film silicon photodiodes with integrated
fluorescence filters”, Biosens. Bioelectron. 52, 232-238 (2014)
20 29 13 Annual Report
Research Areas and Interests
Research Scientist at the BioEngineering Research Group (BERG), based in the Institute for Biotechnolo-
gy and Bioengineering (IBB), Centre for Biological and Chemical Engineering at I.S.T. His research areas
focus on the development of bioanalytical methods and biosensors integrated in FIA systems and lab-on-a
-chip devices for monitoring pathogens, toxic pollutants, and biological compounds. The development of
nano/micro-biocatalysts (biocomposites) mostly based on hydrogels containing protein/cell assemblies
and encapsulating nano-magnetic particles resulting as biocomposites used as nano/micro-biocatalysts is
another field of research.
Recent Selected Publications
F.R.R. Teles, L.P. Fonseca, “The contribution of smart materials and clinical diagnostic micro-devices on
the progress and improvement of human health care” in “Advanced Healthcare Nanomaterials” Editor
Ashutosh Tiwari, WILEY-Scrivener Publishing LLC, USA., 2014, chapter 6, in press
A.P.D. de Lima, E.M. Aschenbrenner, S.N. Oliveira, J.B. Doucet, C.K. Weiss, U. Ziener, L.P. Fonseca,
N.M.P.S. Ricardo, L.L. de Freitas, C.L. Petzhold, K. Landfester “Towards regioselective enzymatic hydrol-
ysis and glycerolysis of tricaprylin in miniemulsion and the direct preparation of polyurethane from the hy-
drolysis products”, J. Mol. Catal. B: Enzym, 98, 127–137 (2013)
F.R.R. Teles, M.L. Martins, M. R. Vieira, Nanotechnology for the diagnosis of parasitic infections” in Nano-
technology in Dermatology, Eds Adman nasir, Adam Firelman and Steven Wang, Springer 2013, chapter
20, pp 209-219
S.A.M. Martins, V.C. Martins, F.P. Cardoso, P.P. Freitas, L.P. Fonseca “Waterborne Pathogen Detection
Using a Magnetoresistive Immuno-Chip” Ed. S. M. Tiquia-Arashiro in Molecular Biological Technologies
for Ocean Sensing, Springer Protocols Handbooks 2012, chapter 13, pp 263-288
Luis P. Fonseca
Ph.D. Instituto Superior Técnico, 1995 Associate Professor with Habilitation
Phone: +351-218419139 e-mail: [email protected]
Research Areas and Interests
Dr. Menezes is Professor at IST (Technical University of Lisbon, Habilitation in 2005) and a Senior Re-
searcher at the Institute for Biotechnology and Bioengineering (IBB, TUL). His work deals with the devel-
opment and use of several systems engineering tools in diverse processing industries with a stronger fo-
cus in the bio/pharmaceutical areas, namely Process Analytical Technologies (PAT), Industrial Chemo-
metrics (IC), Multivariate Data Analysis (MVDA), Multivariate Statistics Process Control (MSPC) and Quali-
ty by Design (QbD). Main research areas are: Process Analytical Technology; Whole Process/Product
Design; Systems Engineering Applied to Manufacturing; and Pharmaceutical Engineering.
Recent Selected Publications
Patent WO 2012/059520 A1 “Spectroscopic finger-printing of raw-materials”, Hoffmann-La Roche AG
(Pub. May 10, 2012). Hakemeyer C, Strauss U, Werz S, Jose GE, Folque F, Menezes JC
Alcalà, M., Blanco, M., Menezes, J. C., Felizardo, P. M., Garrido, A., Pérez, D., Zamora, E., Pasquini, C.
and Romañach, R. J. (2012). Near-Infrared Spectroscopy in Laboratory and Process Analysis. Encyclope-
dia of Analytical Chemistry. (Review, 46 pgs), Wiley DOI:10.1002/9780470027318.a9361
Hakemeyer C, Strauss U, Werz S, Jose GE, Folque F, Menezes JC, “At-line NIR Spectroscopy as Effec-
tive PAT Monitoring Technique in Mab Cultivations During Process Development and Manufacturing”, Ta-
lanta 90, 12–21 (2012)
Lourenco V, Lochmann D, Reich G, Menezes JC, Herdling T, Schewitz J (2012), A Quality by Design
study applied to an industrial pharmaceutical fluid bed granulation. Eur. J. Pharm. Biopharm. 81(2), 438–
447.
Möltgen CV, Puchert T, Menezes JC, Lochmann D, Reich G (2012), A novel in-line NIR spectroscopy ap-
plication for the monitoring of tablet film coating in an industrial scale process. Talanta 92, 26-37.
Preisner OE, Menezes JC, Guiomar R, Machado J, Lopes JA (2012), Discrimination of Salmonella enter-
ica serotypes by Fourier transform infrared spectroscopy. Food Res. Int. 45(2),1058-1064.
José Menezes Ph.D. Instituto Superior Técnico, 1996 Assistant Professor with Habilitation Phone: +351-218417347 e-mail: [email protected]
20 31 13 Annual Report
Claudia Lobato da Silva
Ph.D. Instituto Superior Técnico, 2006 Assistant Professor
Phone: +351-218419591 e-mail: [email protected]
Research Areas and Interests
Current research interests are focused on the ex-vivo expansion of human stem cells, Cellular Therapies
with human adult stem cells, isolation and purification of stem cells, and bioreactors for stem cell culture.
In particular, I have been focused on establishing optimal conditions for the maximization of the expansion
of umbilical cord blood-derived hematopoietic stem/progenitor cells, as well as developing bioreactor strat-
egies for the clinical-scale production of mesenchymal stem/stromal cells from different human sources.
Recent Selected Publications
Ribeiro, A., Laranjeira, P., Mendes, S., Velada, I., Leite, C., Andrade, .P, Santos, F., Henriques, A., Grãos,
M., Cardoso, C.M., Martinho,A., Pais, M., da Silva, C., Cabral, J., Trindade, H., Paiva, A., “Mesenchymal
stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to sup-
press peripheral blood B, natural killer and T cells”, Stem Cell Res Ther 15;4(5):125 (2013)
dos Santos, F., Andrade, P.Z., da Silva, C.L., Cabral, J.M.S., “Bioreactor design for clinical-grade expan-
sion of stem cells”, Biotechnol. J., 8(6), 644-654 (2013)
Andrade, P.Z., de Soure, A.M., dos Santos, F., Paiva, A., Cabral J.M.S., da Silva, C.L., “Ex vivo expansion
of cord blood haematopoietic stem/progenitor cells under physiological oxygen tensions: clear-cut effects
on cell proliferation, differentiation and metabolism” J. Tissue Eng. Regen. Med. DOI: 10.1002/term.1731
(2013)
Andrade, P.Z., dos Santos, F., Cabral, J.M.S., da Silva, C.L., “Stem cell bioengineering strategies to widen
the therapeutic applications of haematopoietic stem/progenitor cells from umbilical cord blood”, J. Tissue
Eng. Regen. Med. DOI: 10.1002/term.1741 (2013)
Boura, J.S., dos Santos, F., Gimble, J.M., Cardoso, C.M., Madeira, C., Cabral, J.M., da Silva, C.L., “Direct
head-to-head comparison of cationic liposome-mediated gene delivery to mesenchymal stem/stromal cells
of different human sources: a comprehensive study”, Hum. Gene Ther. Methods, 24(1), 38-48 (2013)
Simões, I.N., Boura, J.S., dos Santos, F., Andrade, P.Z., Cardoso, C.M.P., Gimble, J.M., da Silva, C.L.,
Cabral, J.M.S., “Human mesenchymal stem cells from the umbilical cord matrix: Successful isolation and
ex vivo expansion using serum-/xeno-free culture media”, Biotechnol. J., 8(4):448-58 (2013)
Gabriel Monteiro Ph.D. Instituto Superior Técnico, 1998 Assistant Professor Phone: +351-218419195 e-mail: [email protected]
Research Areas and Interests
Manufacturing of plasmid- and minicircle-biopharmaceuticals by designing more efficiently expression vec-
tors for its in vivo administration and by engineering of bacterial host strains to improve vectors production.
Recent Selected Publications
J. de la Vega, B. ter Braak, A.R. Azzoni, G.A. Monteiro, D.M.F. Prazeres, “Impact of plasmid quality on
lipoplex-mediated transfection”, J. Pharm. Sci. 102, 3932-3941 (2013)
G.A.L. Gonçalves, D.M.F. Prazeres, G.A. Monteiro, K.L.J. Prather, “De novo creation of MG1655-derived
E. coli strains specifically designed for plasmid DNA production”, Appl. Microbiol. Biotechnol. 97, 611-620
(2013)
S.A.M. Martins, G. Moulas, J.R.C. Trabuco, G.A. Monteiro, V. Chu, J.P. Conde, D.M.F. Prazeres,
“Monitoring intracellular calcium in response to GPCR activation using thin-film silicon photodiodes with
integrated fluorescence filters”, Biosens. Bioelectron. 52, 232-238 (2013)
P.H. Oliveira, D.M.F. Prazeres, G.A. Monteiro, “DNA instability in bacterial genomes: causes and conse-
quences”, in Genome Analysis: Current Procedures and Applications, ISBN: 978-1-908230-29-4; M.S.
Poptsova (ed.) Caister Academic Press, UK, pp 263-285 (2014)
20 33 13 Annual Report
José L. Santos
Ph.D. Instituto Superior Técnico, 1996 Assistant Professor
Phone: +351-218419195 e-mail: [email protected]
Research Areas and Interests
My current research is focused on plasmid DNA (pDNA) manufacturing processes (production, separation, purification, quality control and monitoring) for application in gene therapy or DNA vaccination. The utiliza-tion of membrane processes (ultra and microfiltration) and the development of alternative methods (sonication and microfluidization) to alkaline lysis for plasmid release are under research. The develop-ment of alternative microbial GRAS (generally recognized as safe) platforms for pDNA production will be other goal of my research.
Recent Selected Publications
D.M.F. Prazeres, J.A.L. Santos, “Production and Purification of Adenovirus Vectors for Gene Therapy”, Handbook of Pharmaceutical Biotechnology, 1261-1295 (2010)
S. Freitas, S. Canário, J.A.L. Santos, D.M.F. Prazeres, “Alternatives for the intermediate recovery of plas-mid DNA: performance, economic viability and environmental impact”, Biotechnology journal 4 (2), 265-278 (2009)
M.L. Wu, S.S. Freitas, G.A. Monteiro, D.M.F. Prazeres, J.A.L. Santos, “Stabilization of naked and con-densed plasmid DNA against degradation induced by ultrasounds and high‐shear vortices”, Biotechnology and applied biochemistry 53 (4), 237-246 (2009)
S.S. Freitas, J.A.L. Santos, D.M.F. Prazeres, “Plasmid purification by hydrophobic interaction chromatog-raphy using sodium citrate in the mobile phase”, Separation and Purification Technology 65 (1), 95-104 (2009)
M. Ângela Taipa Ph.D. Instituto Superior Técnico, 1997 Assistant Professor Phone: +351-218419065 e-mail: [email protected]
Research Areas and Interests
Biomolecular Engineering: Biomimetics; combinatorial approaches; molecular recognition; synthetic mimic
affinity ligands for identification, separation and stabilization of biomolecules (antibodies, enzymes, plas-
mid DNA)
Nanobiotechnology: Bio-inspired affinity nanoparticles for immunorecognition
Recent Selected Publications
A.C.A. Roque, C.S.O. Silva, M.A. Taipa, “Affinity-based methodologies and ligands for antibody purifica-
tion: Advances and perspectives”, J. Chromatogr. A 1160, 44-55 (2007)
I.T. Sousa, L. Ruiu, C.R. Lowe, M.A. Taipa, “Synthetic affinity ligands as a novel tool to improve protein
stability“, J. Mol. Recognit. 22, 83-90 (2009)
I.T. Sousa, N.M.T Lourenço , C.A.M. Afonso, M.A. Taipa, “Protein Stabilization with a triazine- scaffolded
dipeptide-mimic synthetic affinity ligand”, J. Mol. Recognit. 26,104-112 (2013)
C.S.O. Silva, M. Lansalot, J.Q. Garcia, M.A. Taipa, J.G. Martinho, “Synthesis and characterization of bio-
mimetic nanogels for immunorecognition”, Coll. Surf. B: Biointerfaces 112, 264-271 (2013)
M.A. Taipa, “Immunological Assays: Biotools for High Throughput Screening and Characterisation of Com-
binatorial Libraries”, in: Advances in Combinatorial Chemistry & High Throughput Screening; Chaguturu,
R. (Ed.); Bentham Science Publishers e-book Series, Vol.1, pp. 130-158 (2013)
M.A. Taipa, “Affinity Separation | Rational Design, Synthesis, and Evaluation: Affinity Ligands”, in: Elsevier
Reference Module in Chemistry, Molecular Sciences and Chemical Engineering, Reedijk, J. (Ed), Elsevier,
Waltham (MA): 26-Feb-2014 doi:10.1016/B978-0-12-409547-2.10738-3
20 35 13 Annual Report
M. Margarida Diogo
Ph.D. Instituto Superior Técnico, 2004 Assistant Professor
Phone: +351-8419591 e-mail: [email protected]
Research Areas and Interests
Current research interests include bioprocessing strategies for expansion and controlled differentiation of pluripotent and neural stem cells and purification of their derivatives envisaging applications in Regenera-tive Medicine and drug discovery and their integration with microscale culture systems to explore the effect of microenvironmental factors on stem cell fate.
Recent Selected Publications
T.G. Fernandes, M.M. Diogo, J.M.S. Cabral, "Stem Cell Bioprocessing: For Cellular Therapy, Diagnostics
and Drug Development", Woodhead Publishing Series in Biomedicine No. 40, UK, pp. 250 (2013)
M.M. Diogo, C. Lobato da Silva, J.M.S. Cabral, “Separation technologies for stem cell bioprocessing”, in Cell Engineering, Volume 8: Stem Cells and Cell Therapy (Mohamed Al-Rubeai and Mariam Naciri, Edi-tors), Springer, [publication date: October 2013]
C.A.V. Rodrigues, T.G. Fernandes, M.M. Diogo, C. Lobato da Silva, J.M.S. Cabral, Bioreactors for Stem Cell Expansion and Differentiation, in Stem Cell Engineering: Principles and Practices (Schaffer D, Bronzi-no JD and Peterson DR, Editors), CRC Press (2013), pp 10.1-10.28
C. Madeira, C.A. Rodrigues, M.S. Reis, F.F. Ferreira, R.E. Correia, M.M. Diogo, J.M.S. Cabral, “Nonviral gene delivery to neural stem cells with minicircles by microporation”, Biomacromolecules, 14(5):1379-87 (2013)
G.N.M. Rodrigues, A.F.S. Matos, T.G. Fernandes, C.A.V. Rodrigues, M. Peitz, S. Haupt, M.M. Diogo, O. Brüstle, J.M.S. Cabral, “Integrated Platform for Production and Purification of Human Pluripotent Stem Cell-derived Neural Precursors”, Stem Cell Rev. Rep., in press, D.O.I. 10.1007/s12015-013-9482-z.
T.G. Fernandes, C.A.V. Rodrigues, M.M. Diogo, J.M.S. Cabral, “Stem cell bioprocessing for Regenerative Medicine”, J. Chem. Technol. Biotechnol., in press, DOI: 10.1002/jctb.4189
A. Fernandes-Platzgummer, M.M. Diogo, C. Lobato da Silva, J.M.S. Cabral, “Maximizing mouse embryon-ic stem cell production in a stirred tank reactor by controlling dissolved oxygen concentration and continu-ous perfusion operation”, Biochem. Eng. J. 82, 81-90 (2014)
Marilia Mateus Ph.D. Instituto Superior Técnico, 1994 Assistant Professor Phone: +351-218419136 e-mail: [email protected]
Research Areas and Interests
Focus on the application of synthetic membranes to bioengineering fields, entailing membrane processing
(membrane crossflow filtration and membrane chromatography), modification of the surface of membranes
(for biocompatibility and selective adsorption capacity), and membrane bioreactors. Recent research pro-
jects address the development of membrane adsorbers and membrane chromatography for the purifica-
tion of protein and plasmid biopharmaceuticals and the characterization of nanoparticles designed for de-
livery of plasmids.
Recent Selected Publications
L. Raiado-Pereira, D.M.F. Prazeres, M. Mateus, “Impact of plasmid size on the purification of model plas-
mid DNA vaccines by phenyl membrane adsorbers”, J. Chromatogr. A 1315, 145-15 (2013).
M.E. Monteiro, L. Raiado-Pereira, D.M.F. Prazeres, M. Mateus, “FRAP biophysical tool to probe nucleic
acids membrane ligand interactions in pDNA purification”, 9th European Biophysics Congress |
EBSA2013, Lisbon, Portugal, 13-17 July (2013).
L. Raiado-Pereira, J. de la Vega, D.M.F. Prazeres, M. Mateus, “Impact of plasmid size on the purification
of model pDNA vaccines by HIC on phenyl membrane adsorbers”, oral communication to the International
Symposium on the Separation of Proteins, Peptides and Polynucleotides | ISPPP 2013, Boston, USA, 17-
19 July (2013).
L. Raiado-Pereira, J. de la Vega, D.M.F. Prazeres, M. Mateus, “Purification of pharmaceutical grade plas-
mid DNA by HIC membrane chromatography – Impact of plasmid size and process throughput”, oral com-
munication to the Portuguese Congress of Microbiology and Biotechnology| Microbiotec’2013, Aveiro, Por-
tugal, 6-8 December (2013).
20 37 13 Annual Report
Carla C.C.R. Carvalho
Ph.D. Instituto Superior Técnico, 2003 Principal Research Scientist
Phone: +351-218419594 e-mail: [email protected]
Research Areas and Interests
Formation of persister cells. Effect of toxic compounds and stressful conditions on cellular membranes and
cell surface properties of bacteria and mechanisms of bacterial adaptation. Prevention and eradication of
biofilms. Fluorescence microscopy and image analysis to assess cell physiology and morphology. Produc-
tion of compounds with marine bacteria. Biotransformation and design of bioreactors for the production of
high-value compounds from low-value substrates in organic:aqueous systems using whole cells.
Recent Selected Publications
C.C.C.R de Carvalho, M.J. Caramujo, “Bacterial diversity assessed by cultivation-based techniques show
predominance of Staphylococccus species on coins collected in Lisbon and Casablanca”, FEMS Microbi-
ology Ecology. doi: 10.1111/1574-6941.12266 (in press). (DOI: 10.1111/1574-6941.12266)
M.J. Caramujo, C. Cunha, C.C.C.R de Carvalho, C. Luís, “Trapped in the pond”, Museus da Universidade
de Lisboa, Lisboa, pp.32. ISBN 978-989-98300-2-8 (2013).
J.M.B.T. Cavalheiro, M.C.M.D. de Almeida, M.M.R. da Fonseca, C.C.C.R de Carvalho, “Adaptation of Cu-
priavidus necator to conditions favoring polyhydroxyalkanoate production”, Journal of Biotechnology 164,
309-317 (2012). (DOI:10.1016/j.jbiotec.2013.01.009)
C.C.C.R. de Carvalho,” Adaptation of Rhodococcus erythropolis cells for growth and bioremediation under
extreme conditions”, Research in Microbiology 163, 125-136 (2012). (DOI: 10.1016/j.resmic.2011.11.003)
C.C.C.R. de Carvalho, M.J. Caramujo, “Lipids of prokaryotic origin at the base of marine food webs”, Ma-
rine Drugs 10, 2698-2714 (2012) (DOI:10.3390/md10122698).
Patent: C.C.C.R. de Carvalho, M.P.C. Marques, “Dispositivo para diluições sucessivas em microplacas”,
PT105887 (2013) (priority date: 14 September 2011).
Frederico Ferreira
Ph.D. Imperial College London, 2004 Principal Research Scientist Phone: +351-218419598 e-mail: [email protected]
Research Areas and Interests
Member of the BioEngineering Research Group at Institute for Biotechnology and Bioengineering. My cur-
rent research interests, balance between fundamental and applied research, with potential translation into
the market of sustainable products and processes. The three current research lines aim at the develop-
ment of new processes, reactors and materials, with an emphasis on membrane based systems, for (i)
tailored materials to mimicking stem cell microenvironments, (ii) advanced separations in pharmaceutical
industry and (iii) biorefineries for sustainable aviation biofuels and added value products.
Recent Selected Publications
G. Székely, J. Bandarra, W. Heggie*, F.C. Ferreira, “Environmental and economic analysis for selection
and engineering sustainable API degenotoxification processes”, Green Chem. 15, 210-225 (2013)
Patent: C.S, Fonseca, N.F. Faria, F.C. Ferreira "Processos para a produção de glicolípidos microbianos
do tipo manosileritritolípidos, a partir de materiais lenhocelulósicos e suas aplicações", Instituto Superior
Técnico, Universidade Técnica de Lisboa, Laboratório Nacional de Energia e Geologia, PT 106959 (2013)
(priority date: 17 May 2013)
C.S Moura., S. Biscaia, T. Viana,, P. J. Bartolo, C. L. Silva, J. S. Cabral, F. C. Ferreira, “Adhesion, prolifer-
ation and distribution of human mesenchymal stem/stromal cells (MSCs) in poly(caprolactone) (PCL) scaf-
folds with different pore sizes”, in High Value Manufacturing – Advanced Research in Virtual and Rapid
Prototyping, Edited by P.J. Bártolo et al, CRC Press, 2014 (ISBN: 978 1 138 00137 4)
G. Székely, J. Bandarra, W. Heggie, B. Sellergren, F.C. Ferreira “Organic solvent nanofiltration: A platform
for removal of genotoxins from active pharmaceutical ingredients”, J. Membrane Sci, 381 (1-2), 21-33
(2011)
L.C. Branco, F.C. Ferreira, J.L. Santos, J.G. Crespo, C.A.M. Afonso, "Sharpless asymmetric dihydroxyla-
tion of olefins in water-surfactant media with recycling of the catalytic system by membrane nanofiltration”,
Adv Synth Catal, 350, 2086 – 2098 (2008)
R.Valadez-Blanco, F.C. Ferreira, R.F. Jorge, A.G. Livingston “A membrane bioreactor for biotransfor-
mations of hydrophobic molecules using organic solvent nanofiltration (OSN) membranes” J Membrane
Sci, 317, 50–64 (2008)
20 39 13 Annual Report
Ana M. Azevedo
Ph.D. Instituto Superior Técnico, 2004 Research Scientist
Phone: +351-218419598 e-mail: [email protected]
Research Areas and Interests
Research Scientist of the Bioseparation Engineering Laboratory (BEL) of the Bioengineering Research
Group (member of the Associated Laboratory IBB – Institute for Biotechnology and Bioengineering). Cur-
rent research interests include the development alternative downstream processes for the purification of
biopharmaceutical biomolecules, including monoclonal antibodies, recombinant proteins, plasmid DNA
and bionanoparticles such as virus and VLPs. A key feature of these novel processes is that they should
allow for scalable and integrated purification platforms. Another focus of my research is the development
of animal cell factories for the production of monoclonal antibodies based on Chinese hamster ovary cells
(or alternatively hybridoma cells).
Recent Selected Publications
P.A.J. Rosa, A.M. Azevedo, S. Sommerfeld, W. Bäcker, M.R. Aires-Barros, "Continuous purification of
antibodies from cell culture supernatant: from concept to process", Biotechnol. J., 8, 352-362 (2013)
L. Borlido, L. Moura, A.M. Azevedo, A.C.A. Roque, M.R. Aires-Barros, J.P.S. Farinha, "Stimuli-Responsive
Magnetic Nanoparticles for Monoclonal Antibody Purification", Biotechnol. J., 8, 709-717 (2013)
L. Borlido, A.M. Azevedo, A.C.A. Roque, M.R. Aires-Barros, "Magnetic separations in biotechnology", Bio-
technol. Adv., 31, 1374–1385 (2013)
R.N. D‘Souza, A.M. Azevedo, M.R. Aires-Barros, N.L. Krajnc, P. Kramberger, M.L. Carbajal, M. Grasselli,
R. Meyer, M. Fernández-Lahore, “Emerging technologies for the integration and intensification of down-
stream bioprocesses”, Pharm. Bioprocess., 1, 423-440 (2013)
A.G. Gomes, A.M. Azevedo, M.R. Aires-Barros, D.M.F. Prazeres, “Validation and scale-up of plasmid DNA
purification by phenyl-boronic acid chromatography”, J. Sep. Sci., 35, 3190–3196 (2012)
D.F.C. da Silva, A.M. Azevedo, P. Fernandes, V. Chu, J.P. Conde, M.R. Aires-Barros, “Design of a micro-
fluidic platform for monoclonal antibody extraction using an aqueous two-phase system”, J. Chromatogr.
A, 1249, 1-7 (2012)
Pedro Fernandes Ph.D. Instituto Superior Técnico, 1999 Research Scientist Phone: +351-218419594 e-mail: [email protected]
Research Areas and Interests
Current research interests focus on bioprocess intensification through miniaturization. Emphasis is given
to the development of enzymatic and whole cell based processes within the pharmaceutical and food and
feed areas, and in the production of chemicals from renewable resources. Pedro also has a distinct inter-
est in the immobilization of enzymes and whole microbial cells.
Recent Selected Publications
M.A.P. Nunes, P.C.B. Fernandes, M.H.L. Ribeiro, “Microtiter plates versus stirred mini-bioreactors in bio-
catalysis: A scalable approach”, Bioresource Technol. 136, 30-40 (2013).
J.A. Figueira, H.H. Sato, P. Fernandes, “Establishing the feasibility of using β-glucosidase entrapped in
Lentikats® and in sol-gel supports for cellobiose hydrolysis”, J. Agric. Food Chem. 61, 626-634 (2013).
E. Aguiar-Oliveira, P. Fernandes, J.M.S. Cabral, F. Maugeri, “Characterisation of biocatalysts immobilised
in niobium—a new inorganic solid support”, Canadian J. Chem. Eng. 91, 432–440(2013).
F.J. Contesini, J.A. Figueira, H.Y. Kawaguti, P.C.B. Fernandes, P.O. Carvalho, M.G. Nascimento, H.H.
Sato, “Potential Applications of Carbohydrases Immobilization in the Food Industry”, Int. J. Mol. Sci. 14,
1335-1369 (2013).
E.M. Ribeiro, P. Fernandes, “Coated-wall mini reactor for inulin hydrolysis”, Current Biotechnol. 2, 47-52
(2013).
F. Carvalho, P. Paradiso, P. Fernandes, A microscopic perspective of a microreactor. Microsc. Microanal.
19, Suppl. 4, 33-34 (2013).
20 41 13 Annual Report
T. Catarina Madeira
Ph.D. Instituto Superior Técnico, 2005 Research Scientist
Phone: +351-210407054 e-mail: [email protected]
Research Areas and Interests
Research Scientist at Stem Cell Bioengineering and Regenerative Medicine Laboratory. Current research
interest is focused on setting-up gene delivery strategies for stem cells expansion, differentiation or for
being used as drug delivery vehicles, specially using non-viral vectors such as plasmids or minicircles as-
sociated with cationic liposomes or physical methods.
Recent Selected Publications
A. Santhagunam, F. dos Santos, C. Madeira, J. Salgueiro, J.M.S. Cabral, “Isolation and ex-vivo expansion
of Synovial Mesenchymal Stromal Cells for Cartilage Repair” Cytotherapy in press (2014)
C. Madeira, C.A.V. Rodrigues, M.S.C. Reis, F.C.G. Ferreira, R.E.S.M. Correia, M.M. Diogo, J.M.S. Cabral,
“Non-viral gene delivery to neural stem cells with minicircles by microporation,” Biomacromolecules 14
1251-1710 (2013)
J. Boura, F. dos Santos, J.M. Gimble, C.M.P. Cardoso, C. Madeira, J.M.S. Cabral, C.L. da Silva, "Direct
head-to-head comparison of cationic liposome-mediated gene delivery to mesenchymal stem/stromal cells
of different human sources: a comprehensive study," Human Gene Therapy Methods 24, 38-48 (2013)
S. Ribeiro, J. Mairhofer, C. Madeira, M. Diogo, C.L. da Silva, G. Monteiro, R. Grabherr, J.M. Cabral,
“Plasmid DNA size does affect non-viral gene delivery efficiency in stem cells”, Cellular Reprogramming
14, 130-137 (2012)
C. Madeira, F. dos Santos, P.Z. Andrade, C.L. da Silva, J.M.S. Cabral, “Mesenchymal stem cells for cellu-
lar therapies”, Stem cells and cancer stem cells, Springer Edition 3, 179-187 (2012)
Scientific Output
2013 BERG Annual Report
Articles
Proceedings
Book Chapters
Invited Oral Communications
Oral Communications
Poster Communications
Dissertations
Books
Patents
Articles in Peer-reviewed Journals
Aguiar-Oliveira, E., Fernandes, P., Cabral, J.M.S.,
Maugeri, F., “Characterisation of biocatalysts immo-
bilised in niobium—a new inorganic solid support”,
Canadian J. Chem. Eng., 91, 432–440
Almeida-Porada, G, Soland, M, Boura, J, Porada,
CD., “Regenerative medicine: prospects for the
treatment of inflammatory bowel disease”. Regen.
Med., 8, 631-44
Borlido, L., Moura, L., Azevedo, A.M., Roque,
A.C.A., Aires-Barros, M.R., Farinha, J.P.S., “Stimuli-
Responsive magnetic nanoparticles for monoclonal
antibody purification”, Biotechnol. J., 8, 709-717
Borlido, L., Azevedo, A.M., Roque, A.C.A., Aires-
Barros, M.R., “Magnetic separations in biotechnolo-
gy”, Biotechnol. Adv., 31, 1374-1385
Boura, J.S., dos Santos, F., Gimble, J.M., Cardoso,
C.M., Madeira, C., Cabral, J.M., da Silva, C.L.,
“Direct head-to-head comparison of cationic lipo-
some-mediated gene delivery to mesenchymal
stem/stromal cells of different human sources: a
comprehensive study”, Hum. Gene Ther. Methods,
24, 38-48
Campenni, L., Nobre, B.P., Santos, C.A., Oliveira,
A.C., Aires-Barros, M.R., Palavra, A.M.F., Gouveia,
L., “Carotenoid and lipid production by the auto-
trophic microalga Chlorella protothecoides under
nutritional, salinity, and luminosity stress condi-
tions”, Appl. Microbiol. Biotechnol., 97, 1383-1393
Carvalho, F., Paradiso, P., Fernandes, P., “A mi-
croscopic perspective of a microreactor”, Microsc.
Microanal., 19, 33-34
Contesini, F.J., Figueira, J.A., Kawaguti, H.Y., Fer-
nandes, P.C.B., Carvalho, P.O., Nascimento, M.G.,
Sato, H.H., “Potential applications of carbohydrases
immobilization in the food industry”, Int. J. Mol. Sci.,
14, 1335-1369
de Carvalho, R.N.L., Lourenço, N.M.T., Gomes,
P.M.V., da Fonseca, L.J.P., “Swelling behavior of
gelatin-ionic liquid functional polymers”, J. Polym.
Sci., Part B: Polym. Phys., 51, 817-825
Cavalheiro, J.M.B.T.,de Almeida, M.C.M.D., da Fon-
seca, M.M.R., de Carvalho, C.C.C.R. “Adaptation of
Cupriavidus necator to conditions favoring polyhy-
droxyalkanoate production”. J. Biotechnol. 164, 309
–317.
Donato, S.S., Chu, V., Prazeres, D.M.F., Conde,
J.P., “Metabolic viability of Escherichia coli trapped
by dielectrophoresis in microfluidics”, Electrophore-
sis, 34, 575-582
D`Souza, R.N., Azevedo, A.M., Aires-Barros, M.R.,
Krajnc, N.L., Kramberger, P., Carbajal, M.L.,
Grasselli, M., Meyer, R., Fernández-Lahore, M.,
“Emerging technologies for the integration and the
intensification of bioprocesses”, Pharm. Biopro-
cess., 1, 423-440
Figueira, J.A., Sato, H.H., Fernandes, P.,
“Establishing the feasibility of using β-glucosidase
entrapped in Lentikats® and in sol-gel supports for
cellobiose hydrolysis”, J. Agric. Food Chem., 61,
626-634
Gonçalves, G.A.L., Prazeres, D.M.F., Monteiro,
G.A., Prather, K. L. J., “De novo creation of MG1655
-derived E. coli strains specifically designed for plas-
mid DNA production”, Appl. Microbiol. Biotechnol.,
97, 611-620
Hakemeyer, C., Strauss, U., Werz, S., Folque, F.,
Menezes, J.C., “Near-infrared and two-dimensional
fluorescence spectroscopy monitoring of monoclo-
nal antibody fermentation media quality: Aged me-
dia decreases cell growth”, Biotechnol. J., 8, 835-
846
de Lima, A.P.D., Aschenbrenner, E.M., Oliveira,
S.N., Doucet, J-B., Weiss, C.K., Ziener, U., Fonse-
ca, L.P., Ricardo, N.M.P.S., Freitas, L.L., Petzhold,
C.L., Landfester, K., “Towards regioselective enzy-
matic hydrolysis and glycerolysis of tricaprylin in
miniemulsion and the direct preparation of polyure-
thane from the hydrolysis products”, J. Mol. Catal.
B: Enzym., 98, 127-137
Madeira, C., Rodrigues, C.A.V., Reis, M.S.C., Fer-
reira, F.F.C.G., Correia, R.E. S. M., Diogo, M.M.,
Cabral, J.M.S., "Nonviral gene delivery to neural
stem cells with minicircles by microporation”, Biom-
acromolecules, 14, 1379-1387
Madeira, P.P., Bessa, A., Alvares-Ribeiro, L., Aires-
Barros, M.R., Rodrigues, A.E., Zaslavsky, B.Y.,
“Analysis of amino acid-water interactions by parti-
tioning in aqueous two-phase systems. I-Amino ac-
ids with non-polar side-chains”, J. Chromatogr. A,
1274, 82-86
Madeira, P.P., Bessa, A., de Barros, D.P.C., Teixei-
ra, M.A., Alvares-Ribeiro, L., Aires-Barros, M.R.,
Rodrigues, A.E., Chait, A., Zaslavsky, B.Y.,
“Solvatochromic relationship: Prediction of distribu-
tion of ionic solutes in aqueous two-phase systems”,
J. Chromatogr. A, 1271, 10-16
Madeira, P.P., Bessa, A., Teixeira, M.A., Alvares-
Ribeiro, L., Aires-Barros, M.R., Rodrigues, A.E.,
Zaslavsky, B.Y., “Study of organic compounds-
water interactions by partition in aqueous two-phase
systems”, J. Chromatogr. A, 1332, 97-104
Publications
20 45 13 Annual Report
Martins, D.C., Chu, V., Prazeres, D.M.F., Conde,
J.P., “Streaming currents in microfluidics with inte-
grated polarizable electrodes”, Microfluid. Nanoflu-
id., 15, 361-376
Moreira, F., Badenes, S.M., Cabral, J.M.S.,
“Biocatalytic transesterification of triglycerides and
alcohols for the production of biodiesel using cu-
tinase in organic media”, Biocatal. Biotransform., 31,
246-254
Novo, P., Moulas, G., Prazeres, D.M.F., Chu, V.,
Conde, J.P., “Detection of ochratoxin A in wine and
beer by chemiluminescence-based ELISA in micro-
fluidics with integrated photodiodes”, Sens. Actua-
tors B, 176, 232-240
Nunes, M.A.P., Fernandes, P.C.B., Ribeiro, M.H.L.,
“Microtiter plates versus stirred mini-bioreactors in
biocatalysis: A scalable approach”, Bioresource
Technol., 136, 30-40
Oliveira, P.H., Boura, J.S., Abecasis, M.M., Gimble,
J.M., da Silva, C.L., Cabral, J.M.S., “Impact of hy-
poxia and long-term cultivation on the genomic sta-
bility and mitochondrial performance of ex-vivo ex-
panded human stem/stromal cells”, Stem Cell Res.,
9, 225-236
Oliveira, P.H., da Silva, C.L., Cabral, J.M.S., “An
appraisal of human mitochondrial DNA instability:
new insights into the role of non-canonical DNA
structures and sequence motifs”, PLoS One, 8,
e59907
Raiado-Pereira, L., Prazeres, D.M.F., Mateus, M.,
“Impact of plasmid size on the purification of model
plasmid DNA vaccines by phenyl membrane ad-
sorbers”, J. Chromatogr. A, 1315, 145-151
Ribeiro, A., Laranjeira, P., Mendes, S., Velada, I.,
Leite, C., Andrade, P., Santos, F., Henriques, A.,
Grãos, M., Cardoso, C.M., Martinho, A., Pais, M., da
Silva, C.L., Cabral, J.M.S., Trindade, H., Paiva, A.,
“Mesenchymal stem cells from umbilical cord matrix,
adipose tissue and bone marrow exhibit different
capability to suppress peripheral blood B, natural
killer and T cells”, Stem Cell Res. Ther., 4:125
Ribeiro, E.M., Fernandes, P., “Coated-wall mini re-
actor for inulin hydrolysis”, Curr. Biotechnol., 2, 47-
52
Rosa, P.A.J., Azevedo, A.M., Sommerfeld, S., Mut-
ter, M., Baecker, W., Aires-Barros, M.R.,
“Continuous purification of antibodies from cell cul-
ture supernatant with aqueous two-phase systems:
From concept to process”, Biotechnol. J., 8, 352-362
dos Santos, F., Andrade, P.Z., da Silva, C.L., Ca-
bral, J.M.S., “Bioreactor design for clinical-grade
expansion of stem cells”, Biotechnol. J., 8, 644-654
Santos, R., Rocha, A., Matias, A., Duarte, C., Sá-
Nogueira, I., Lourenço, N., Borges, J.P., Vidinha, P.,
“Development of Antimicrobial Ion Jelly Fibers”,
RSC Advances, 3, 24400-24405
Silva, C.S.O., Lansalot, M., Garcia, J.Q., Taipa,
M.A., Martinho, J.G., “Synthesis and characteriza-
tion of biomimetic nanogels for immunorecognition”,
Colloids Surf. B, 112, 264-271
Simões, I.N., Boura, J.S., dos Santos, F., Andrade,
P.Z., Cardoso, C.M.P., Gimble, J.M., da Silva, C.L.,
Cabral, J.M.S., “Human mesenchymal stem cells
from the umbilical cord matrix: Successful isolation
and ex vivo expansion using serum-/xeno-free cul-
ture media”, Biotechnol. J., 8, 448-458
Sousa, I.T., Lourenço, N.M.T., Afonso, C.A.M., Tai-
pa, M.A., “Protein stabilization with a dipeptide-
mimic triazine-scaffolded synthetic affinity ligand”, J.
Mol. Recognit., 26, 104-112
Szekely, G., Gil, M., Sellergren, B., Heggie, W., Fer-
reira, F.C., “Environmental and economic analysis
for selection and engineering sustainable API de-
genotoxification processes”, Green Chem., 15, 210-
225
De La Vega, J., Ter Braak, B., Azzoni, A.R., Mon-
teiro, G.A., Prazeres, D.M. F., “Impact of Plasmid
Quality on Lipoplex-Mediated Transfection”, J.
Pharm. Sci., 102, 3932-3941
Vicente, J., Pinto, J., Menezes, J.C., Gaspar, F.,
“Fundamental analysis of particle formation in spray
drying”, Powder Technol., 247, 1-7
Articles in National Journals
Prazeres, D.M.F., "Histórias de Inovação Aberta",
Ingenium, Jul/Ago, 68-71
Simcikova, M., Prazeres, D.M.F., Monteiro, G.A.,
“Design, construção e produção de minicírculos
como vectores de entrega de genes”, Boletim de
Biotecnologia, 4, 28-30
Articles in Conference Proceedings
Monteiro, B.J.C., Guerreiro, J.D.T., dos Santos, F.,
Cabral, J.S.M., da Silva, C.L., Ferreira, F.C., “Study
of the Effects of Electrospun Poly(epsloncapro-
lactone)/Gelatin Matrices on Human Mesenchymal
Stem Cell Culture”, IEEE 3rd Portuguese Bioengi-
neering Meeting | ENBENG 2013, Univ. Minho, Bra-
ga, February
Carvalho, F., Marques, M.P.C., Fernandes, P.
“Continuous sucrose hydrolysis in microchannel
reactors”, 2nd International Conference on Imple-
mentation of microreactor technology into biotech-
nology | IMTB 2013, Cavtat, Croatia, May
Books
Caramujo M.J., Cunha C., de Carvalho, C.C.C.R.,
Luís, C. “Trapped in the pond”. Publisher: Museus
da Universidade de Lisboa, Lisboa, pp.32. ISBN
978-989-98300-2-8
Fernandes, T.G., Diogo, M.M., Cabral, J.M.S.,
“Stem Cell Bioprocessing: For Cellular Therapy,
Diagnostics and Drug Development”, Biohealthcare
Publishing, Cambridge, pp.236. ISBN: 978-1-
907568-88-6
Book Chapters
BadenesBadenes, S.M., Ferreira, F.C., Cabral,
J.M.S., “Membrane bioreactors for biofuel produc-
tion”, in: “Separation and Purification Technologies
in Biorefineries”, S. Ramaswamy, H.-J. Huang and
B.V. Ramarao (Eds.), Wiley, Chichester, 377-407
Diogo, M.M., da Silva, C.L., Cabral, J.M.S.,
“Separation technologies for stem cell biopro-
cessing”, in: Cell Engineering, Volume 8: Stem Cells
and Cell Therapy, M. Al-Rubeai and M. Naciri (Eds),
Springer, Dordrecht, 157-181
Fernandes, P., Cabral, J.M.S., “Production of
Sweeteners”, in: Biotechnology in Agriculture and
Food Processing: Opportunities and Challenges,
P.S. Panesar, and S.S. Marwaha. (Eds.), CRC
Press, Boca Raton, Florida, 387-415
Fernando S.R.R., Teles, M.L.M., Vieira, M.R., Fon-
seca, L.P., “Nanotechnology for the diagnosis of
parasitic infections” in: Nanotechnology in Dermatol-
ogy, A. Nasir, A. Firelman and S. Wang (Eds),
Springer, Dordrecht, 209-219
Rodrigues, C.A.V., Fernandes, T.G., Diogo, M.M.,
da Silva, C.L., Cabral, J.M.S., “Bioreactors for Stem
Cell Expansion and Differentiation”, in: Stem Cell
Engineering: Principles and Practices, D. Schaffer,
J.D. Bronzino and D.R. Peterson (Eds), CRC Press,
Boca Raton, Florida, 10.1-10.28
dos Santos, F., Andrade, P.Z., da Silva, C.L., Ca-
bral, J.M.S., “Scalling-up ex-vivo expansion of mes-
enchymal stem cells for cellular therapies”, in: Mes-
enchymal Stem Cell Therapy , L. Chase and M.
Vemuri (Eds.), Humana Press, New York, 1-14
Taipa, M.A., “Immunological Assays: Biotools for
High Throughput Screening and Characterisation of
Combinatorial Libraries”, in: Advances in Combina-
torial Chemistry & High Throughput Screening, R.
Chaguturu (Ed); Bentham Science Publishers, 130-
158
Patents
Fonseca, C.S, Faria, N.F, Ferreira, F.C., “Processos
para a produção de glicolípidos microbianos do tipo
manosileritritolípidos, a partir de materiais lenhoce-
lulósicos e suas aplicações”, IST/UL, LNEG, Paten-
te de Invenção Nacional n.º 106959; Priority date:
17 Maio 2013
de Carvalho, C.C.C.R., Marques, M.P.C..
“Dispositivo para diluições sucessivas em micropla-
cas”, PT105887, 8 August 2013 (Priority date: 14
September de 2011)
da Silva, C.L., Cabral, J.M.S., Andrade, P.Z., dos
Santos, F., Almeida-Porada, G. "Processo De Ex-
pansão Ex Vivo De Células Estaminais Em Biorre-
actor", IST/UL, Provisional patent no. 106225; Prio-
rity date: 23 March 2013
Invited Oral Communication
International Conferences
Aires-Barros, M.R., “Aqueous two-phase systems: a
new platform for biopharmaceuticals purification”,
40th International Conference of Slovak Society of
Chemical Engineering, Vysoké Tatry, Slovak Re-
public, May
Azevedo, A.M., Aires-Barros, M.R., “Aqueous Two-
Phase Systems for Bioprocessing Integration”, 20th
Biennial meeting of the International Society for Mo-
lecular Recognition | Affinity 2013, Vienna, Austria,
June
Cabral J.M.S., Bioengineering strategies for ex-vivo
cultivation and purification of human stem cells,
New Directions for Tissue Engineering and Regen-
erative Medicine, Sonoma, California, US, July
Cabral J.M.S., Bioengineering strategies for ex-vivo
cultivation and purification of human stem cells, Ox-
ford Global Stem Cell Congress, London, UK, No-
vember
Fonseca, L.P., “Emulsions and nanoparticles on
innovative biocatalysis, design of drug delivery and
cell-free protein expression systems“, XXI Interna-
tional Conference on Bioencapsulation, Berlin, Ger-
many, August
Menezes JC, The PAT toolbox & skills set, 9th. Kol-
20 47 13 Annual Report
loquium Prozessanalytik – 100 Years of PAT, BASF
-Ludwigshafen, Germany, November
Menezes JC. A Critical Discussion of EMA's NIR
Draft Guideline on the use of NIRS by the Pharma-
ceutical Industry. IFPAC-2013, Baltimore (MD),
USA, January
da Silva, C.L., “Scalable production of human stem/
progenitor cells in microcarrier-based culture sys-
tems”, Cell Therapy Manufacturing, Brussels, Bel-
gium, December
National Conferences
Azevedo, A.M., Aires-Barros, M.R., “Aqueous Two-
Phase Systems for Antibodies Purification: from
macro to micro-scale”, 8º Encontro Nacional de Cro-
matografia, Universidade da Beira Interior, Covilhã,
Portugal, December
Badenes, S.M., Fernandes, T.G., Pusch, A., Haupt,
S., Rodrigues, C.A.V., Bear, M., Hervy, M., Diogo,
M.M., Brüstle, O. and Cabral, J.M.S., “Evaluation of
microcarrier-based suspension cultures for human
induced pluripotent stem cells”, 8th International
Meeting of the Portuguese Society for Stem Cells
and Cell Therapies, University of Algarve, Faro, Por-
tugal, May
Diogo, M.M., “Integrated Platform for Production
and Purification of Human Pluripotent Stem Cell-
Derived Neural Precursors”, MicroBiotec’13, Univer-
sidade de Aveiro, Aveiro, Portugal, December
Ferreira, F.C., “Tailoring biomaterials to support
stem cell cultivation”, International Advanced
Course on Regenerative Medicine Manufacturing,
Tavira, Algarve, Portugal, Apr-May
Ferreira, F.C., “Electrospinning: Potential for Appli-
cation in Regenerative Medicine”, 3rd Advanced
Course on Regenerative Medicine, Marinha Grande,
Portugal, March
Madeira, C., “Investigação e cartilagem”, 5º Curso
teórico-prático de Cartilagem Articular, Teatro Aber-
to, Lisbon, Portugal, November
Madeira, C., “Nanovectors for widening stem cell-
based therapies”, UL Summer course Lecture Se-
ries, Universidade de Lisboa, Lisbon, Portugal, July
Santhagunam, S., dos Santos, F., Madeira, C., Sal-
gueiro, J., Cabral, J.M.S., “Isolation and ex-vivo ex-
pansion of Synovial Mesenchymal Stromal Cells for
Cartilage Repair”, 5º Curso teórico-prático de Carti-
lagem Articular, Teatro Aberto, Lisbon, Portugal,
November
Oral Communications
International Conferences
Azevedo, A.M., Aires-Barros, M.R., “Integration and
Intensification of Downstream Bioprocessing based
in Aqueous Two-Phase Systems “, 33th Internation-
al Symposium on the Separation of Proteins, Pep-
tides and Polynucleotides | ISPPP, Boston, MA/
USA, July
Azevedo, A.M., Silva, M.F.F., Aires-Barros, M.R., “A
novel approach for mAbs bioprocessing: Clarifica-
tion and capture by aqueous two-phase extraction”,
17th International Conference on Biopartitioning and
Purification | BPP2013, Newport, RH/USA, October
Boura, J.S., Soland, M., Yin, W., Kuo, C., Madeira,
C., da Silva, C.L., Porada, C., Almeida-Porada, G.,
“Gene Delivery Strategies to Efficiently Over-
express HLA-G in Bone Marrow-Derived Mesenchy-
mal Stromal Cells”, MSC 2013, Cleveland, USA,
August (selected from abstracts)
Canadas, R.F., Cavalheiro, J.M.B.T., Guerreiro,
J.D.T., de Almeida, M.C.M.D., Pollet, E., Lobato da
Silva, C., da Fonseca, M.M.R., Ferreira, F.C.,
“Fabrication and application of electrospun fibrous
scaffolds, using polyhydroxyalkanoates bioproduced
from crude glycerol, to support human mesenchy-
mal stem cell cultivation”, European Symposium on
Biopolymers - ESBP2013, Lisbon, Portugal, October
Hatami, J., Andrade, P.Z., Cabral, J.M.S., Lobato da
Silva C., Ferreira, F.C. “A multi-phase protocol for
the expansion and megakaryocytic differentiation of
umbilical cord blood hematopoietic stem/progenitor
cells”, 9th European Congress of Chemical Engi-
neering & 2nd European Congress of Applied Bio-
technology, Hague, The Netherlands, April
Matos, J.C., Domingues, I., Monteiro, G.A., Gon-
çalves, M.C., “Design and production of silica and
ORMOSIL nanoparticles for gene delivery”, Interna-
tional Conference on Chemical and Bioprocess En-
gineering-INDIA, Warangal, Andhra Pradesh, India,
November
Monteiro, M.E., Raiado-Pereira L., Prazeres,
D.M.F., Mateus, M., “FRAP biophysical tool to probe
nucleic acids membrane ligand interactions in pDNA
purification”, 9th European Biophysics Congress |
EBSA2013, Lisbon, Portugal, July
Moura, C.S., Biscaia, S., Viana, T., Bártolo, P.J., da
Silva, C.L., Cabral, J.M.S., Ferreira, F.C.,
“Adhesion, proliferation and distribution of human
mesenchymal stem/stromal cells (MSCs) in Poly(ɛ-
caprolactone) (PCL) scaffolds with different pore
sizes”, International Conference on Advanced Re-
search in Virtual and Rapid Prototyping (VRAP
2013), Leiria, Portugal, October
Pereira, P.M., Moita, A.S., Moreira, A.L.N., Mon-
teiro, G.A., Prazeres, D.M.F., “Characterization of
the Topography and Wettability of Biomimetic Repli-
cas of the Surfaces of Rose Petals and Clover
Leaves”, 4th International Conference in Bionic En-
gineering, Nanjing, China, August
Raiado-Pereira, L., de la Vega, J., Prazeres, D.M.F.,
Mateus, M., “Impact of plasmid size on the purifica-
tion of model pDNA vaccines by HIC on phenyl
membrane adsorbers”, International Symposium on
the Separation of Proteins, Peptides and Polynucle-
otides | ISPPP 2013, Boston, USA, July
Rodrigues, G.M.C., Matos, A.S., Fernandes, T.G.,
Diogo, M.M., Cabral, J.M.S., “Purification of Human
Induced Pluripotent Stem Cell-Derived Neural Pro-
genitors for Regenerative Medicine Applications”,
9th European Congress of Chemical Engineer-
ing/2nd European Congress of Applied Biotechnolo-
gy, The Hague, Netherlands, April (selected from
abstracts)
Rosa, A.M., Louro, A.F., Azevedo, A.M., Martins,
S.A.M., Prazeres, D.M.F. “Molecular Detection of
Nucleic Acids Based on Antibodies Immobilized in
Paper-based Microfluidic Devices via Carbohydrate-
binding Modules”, 20th Biennial meeting of the Inter-
national Society for Molecular Recognition | Affinity
2013, Viena, Austria, June
Šimčíková, M., Prazeres, D.M.F., Prather, K.L.J.,
Monteiro, G.A. “Design of resolvase expression sys-
tems for minicircle production”, 5th PEGS – Proteins
& Antibody Engineering Summit - Europe 2013, Lis-
bon, Portugal, November
National Conferences
Altas, M.C., Fonseca, L.P., Lourenço, N.M.T.,
“Enzymatic Resolution of Secondary Alcohols in
Miniemulsion Media”, 10th Portuguese National
Meeting of Organic Chemistry, Lisbon, September
de Barros, D.P.C., “Prediction of Biomolecules Parti-
tioning in Aqueous Two Phase Systems Using a
Semi - Empirical Approach”, 2nd Portuguese Bio-
molecular Modelling Meeting, Foz do Arelho, April
Boura J.S., Soland M., Yin W., Kuo C., Madeira C.,
da Silva C.L., Porada C., Almeida-Porada G., “Gene
Delivery Strategies to Efficiently Over-express Func-
tional HLA-G in Bone Marrow-Derived Mesenchymal
Stromal Cells” MicroBiotec´13, Aveiro, December
(selected from abstracts)
Carvalho, R.Jr., Woo, J., Aires-Barros, M.R., Cra-
mer, S.M., Azevedo, A.M., “Multimodal behavior of
phenylboronate chromatography”, 8º Encontro Naci-
onal de Cromatografia, Universidade da Beira Inte-
rior, Covilhã, December
Hatami, J., Andrade, P.Z., Cabral, J.M.S., da Silva,
C.L., Ferreira, F.C., “A two-phase protocol for the
expansion and megakaryocytic differentiation of
umbilical cord blood hematopoietic stem/progenitor
cells”, 8th International Meeting of the Portuguese
Society for Stem Cells and Cell Therapies, Faro,
May (Abstract awarded)
Monteiro, B.J.C., Guerreiro, J.D.T., dos Santos, F.,
Cabral, J.S.M., da Silva, C.L., Ferreira, F.C., “Study
of the effects of electrospun poly(epslon-
caprolactone)/gelatin matrices on human mesen-
chymal stem cell culture”, 3rd Portuguese Bioengi-
neering Meeting, Braga, February (Presentation
award: 3rd best Master Thesis)
Raiado-Pereira, L., de la Vega, J., Prazeres, D.M.F.,
Mateus, M., “Purification of pharmaceutical grade
plasmid DNA by HIC membrane chromatography –
Impact of plasmid size and process throughput”,
Portuguese Congress of Microbiology and Biotech-
nology | Microbiotec’2013, Aveiro, December
Silva, D.F.C., Azevedo, A.M., Fernandes, P., Chu,
V., Conde, J.P., Aires-Barros, M.R., “Aqueous two-
phase system in a microfluidic platform to accelerate
bioprocess design and optimization of monoclonal
antibodies”, Portuguese Congress of Microbiology
and Biotechnology | Microbiotec’2013, Aveiro, De-
cember
Šimčíková, M., Prather, K.L.J., Prazeres, D.M.F.,
Monteiro, G.A., “Development of a minicircle pro-
duction system based on ParA resolvase–mediated
in vivo recombination”, Portuguese Congress of
Microbiology and Biotechnology | Microbiotec’2013,
Aveiro, December
de Sousa, M.C. A, Rodrigues, C., Ferreira, I. F.,
Sirgado, T., Diogo, M., da Silva, C. L, Ferreira, F.C.
“Electrospun Nanofiber Based Scaffold Platform for
Stem Cell Alignment”, 1st CLUSTER Workshop in
Materials and Nanotechnology, IST, Lisbon, Decem-
ber
Poster Communications
International Conferences
Altas M.C., Fonseca L.P. Lourenço N.M.T., “Low
Temperature Enzymatic Resolution of 1-
Phenylethanol in Miniemulsion Media”, Biotrans
2013, Manchester, UK, July
Amador, M., Quesada-Hernández, E. Escacena, N.
Hmadcha, A. Ferreira, F.C., Heitor, M.V. Soria, B.
20 49 13 Annual Report
“Towards a new regulatory framework for cellular
medicaments manufacturing and clinical use in Eu-
rope”, I International Meeting on Stem Cells for Re-
generative Medicine and Drug Screening, Biocant,
Cantanhede, Portugal, July
Azevedo A.M., dos Santos, R., Rosa, S.A.S.L.,
Aires-Barros, M.R., “An Alternative Capture Step for
Monoclonal Antibodies: Phenyl Boronate as a New
Multi-modal Ligand”, 33th International Symposium
on the Separation of Proteins, Peptides and Polynu-
cleotides | ISPPP, Boston, MA/USA, July
Badenes, S.M., Fernandes, T.G., Pusch, A., Haupt,
S., Rodrigues, C.A.V., Bear, M., Hervy, M., Diogo,
M.M., Brüstle, O., Cabral, J.M.S., “Evaluation of mi-
crocarrier-based suspension cultures for human
induced pluripotent stem cells”, ECI Conference -
Scale-Up and Manufacturing of Cell-Based Thera-
pies II, San Diego, USA, January
Badenes, S.M., Fernandes, T.G., Pusch, A., Haupt,
S., Rodrigues, C.A.V., Bear, M., Hervy, M., Diogo,
M.M., Brüstle, O., Cabral, J.M.S., "Evaluation of Mi-
crocarrier-based Suspension Cultures for Human
Induced Pluripotent Stem Cells", International Socie-
ty for Stem Cell Research, 11th Annual Meeting,
Boston, USA, June
de Barros, D.P.C., Campos, S.R.R., Madeira, P.P.,
Azevedo, A.M., Baptista, A.M., Aires-Barros, M.R.,
“A semi-empirical model as a tool to predict bio-
molecular partitioning in aqueous two phase sys-
tem”, 20th Biennial meeting of the International So-
ciety for Molecular Recognition | Affinity 2013, Vien-
na, Austria, June
Boura, J.S., Soland, M., Yin W., Kuo, C., Madeira,
C., da Silva, C.L., Porada, C., Almeida-Porada, G.,
“Non-viral Gene Delivery of HLA-G to Bone Marrow
Stem Cells Using Minicircles”, Wake Forest Institute
for Regenerative Medicine Annual Retreat, Winston-
Salem, USA, March
Canadas, R.F., Cavalheiro, J.M.B.T., Guerreiro,
J.D.T., de Almeida, M.C.M.D., Pollet, E., da Silva,
C.L., da Fonseca, M.M.R., Ferreira, F.C.
“Polyhydroxyalkanoates: their production from crude
glycerol, electrospinning in fibrous scaffolds and use
to support mesenchymal stem cells culture”, 9th
European Congress of Chemical Engineering & 2nd
European Congress of Applied Biotechnology,
Hague, The Netherlands, April
Carvalho, R.Jr., Woo, J., Azevedo, A.M., Cramer,
S.M., Aires-Barros, M.R., “Phenylboronic acid as
ligand for a multimodal chromatography: characteri-
zation using protein library”, 20th Biennial meeting
of the International Society for Molecular Recogni-
tion | Affinity 2013, Vienna, Austria, June
Carvalho, R.Jr., Woo, J., Nakamura, K.A., Aires-
Barros, M.R., Azevedo, A.M., Cramer, S.M., “Phenyl
Boronic Acid as Ligand for a Multimodal Chromatog-
raphy: Adsorption Behavior Comparison between
Control Pore Glass and Agarose Matrixes” 33th In-
ternational Symposium on the Separation of Pro-
teins, Peptides and Polynucleotides | ISPPP, Bos-
ton, MA/USA, July
Carvalho, R.Jr., Woo, J., Parimal, S., Aires-Barros,
M.R., Cramer, S.M., Azevedo, A.M., “Phenylboronic
acid as ligand for a multimodal chromatography:
proof of concept”, 20th Biennial meeting of the Inter-
national Society for Molecular Recognition | Affinity
2013, Vienna, Austria, June
Dhadge, V., Azevedo, A., Hussain, A., Aires-Barros,
R., Roque, A.C.A., “Modified magnetic particles
coated with aminophenyl boronic acid for antibody
purification”, 20th Biennial meeting of the Interna-
tional Society for Molecular Recognition | Affinity
2013, Vienna, Austria, June
Hatami, J. Andrade, P.Z., Cabral, J.M.S., da Silva,
C.L, Ferreira, F.C., “Effective megakaryocytic differ-
entiation of umbilical cord blood hematopoietic stem/
progenitor cells using two-phase protocol”, Interna-
tional Twin Congress, 14th Congress on Reproduc-
tive Biomedicine and 9th Congress on Stem Cell
Biology & Technology, Tehran, Iran, September
Magalhães, S., Duarte, S., Monteiro, G.A., Prieto,
M., Fernandes, F., “Plasmid DNA delivery followed
through Förster Resonance Energy Transfer”, 9th
European Biophysics Congress EBSA, Lisbon, Por-
tugal, July
Monteiro, M.E., Raiado-Pereira, L., Prazeres,
D.M.F., Mateus, M., “FRAP as biophysical tool to
probe RNA and pDNA interaction with chromato-
graphic ligands in membrane adsorbers”, 20th Bien-
nial Meeting of the International Society for Molecu-
lar Recognition | Affinity 2013, Vienna, Austria, June
Monteiro, M.E., Raiado-Pereira, L., Prazeres,
D.M.F., Mateus, M., “FRAP Biophysical Tool to
Probe Nucleic Acids Membrane Ligand Interactions
in pDNA Purification in Membrane Adsorbers”, 9th
European Biophysics Congress- EBSA2013, Lisbon,
Portugal, July
Pinto-de-Oliveira, A., Coutinho, A., Ramos, C.G.,
Sousa, S.A., de Carvalho, C.C.C.R., Leitão, J.H., Sá
-Correia, I. “The Burkholderia cepacia small colony
variants (SC V) are a more pathogenic bacterial
form that may facilitate persistent respiratory infec-
tions in CF patients”, 36th European Cystic Fibrosis
Conference, Lisbon, Portugal, June
Rodrigues, G.M.C., Matos, A.S., Fernandes, T.G.,
Diogo, M.M., Cabral, J.M.S., “Purification of Human
Induced Pluripotent Stem Cell-Derived Neural Pro-
genitors for Regenerative Medicine Applications”,
International Society for Stem Cell Research, 11th
Annual Meeting, Boston, USA, June
Rodrigues, G.M.C., Matos, A.S., Fernandes, T.G.,
Diogo, M.M., Cabral, J.M.S., “Purification of Human
Induced Pluripotent Stem Cell-Derived Neural Pro-
genitors for Regenerative Medicine Applications”,
International Conference on Stem Cells for Drug
Screening and Regenerative Medicine, Cantan-
hede, Portugal, July
Sanches, S., Nunes, C., Passarinho, P., Ferreira, F.,
Rodrigues, A., Cardoso, V.V., Ferreira, E., Benoliel,
M.J., Crespo, M.T.B., Pereira, V.J., Crespo, J.G.,
“Evaluation of an Hybrid Process that Combines LP/
UV Photocatalysis with Nanofiltration for Water
Treatment”, 8th Micropol & Ecohazard 2013, Zurich,
Switzerland, June
dos Santos D.J.V.A., Leitão, J.H., Guedes, R.C.,
“Development and validation of a homology model
of Type II phosphomannose isomerase”, 6th Inter-
national Theoretical Biophysics Symposium
(TheoBio 2013), Gothenburg, Sweden, June
dos Santos, F., Costa, R., Burnouf, T., Tseng, Y-H.,
Liu, S-H., Ku, C-P., da Silva, C.L., Cabral, J.M.S.,
“Scalable expansion of human mesenchymal stem
cells using a microcarrier-based system under se-
rum-free and xeno-free conditions”, Scale-Up and
Manufacturing of Cell-Based Therapies, San Diego,
USA, January
da Silva, C.L., dos Santos, F., Campbell, A., An-
drade, P.Z., Wen, Y., Boucher, S., Roos, E., Kuli-
gowski, S., Vemuri, M., Cabral, J.M.S., “A High Den-
sity Xeno-Free Bioreactor Culture System for the
Clinical-Scale Expansion of Human Mesenchymal
Stem/Stromal Cells”, Scale-Up and Manufacturing of
Cell-Based Therapies, San Diego, USA, January
Szekely, Gy., Ferreira, F.C., Heggie, W., Livingston,
A.G., “Process intensification by organic solvent
nanofiltration: removal of genotoxic impurities from
pharmaceutical products”, 4th International Confer-
ence on Organic Solvent Nanofiltration, Aachen,
Germany, March
Trabuco, J.R.C., Willson, R.C, Prazeres, D.M.F.,
“Miniaturization of Capture Assays for Dengue De-
tection in Airports: A Comparative Evaluation of
Available Technologies”, Affinity 2013, Vienna, Aus-
tria, June
Weber, J.L, Carmelo, J.G., Bear, M., Hervy M., Di-
ogo, M.M., da Silva, C.L., Cabral, J.M.S.,
“Evaluation of microcarrier-based suspension cul-
tures for human mesenchymal stem cells”, Biopro-
cess International Conference & Exposition, Boston,
USA, September
National Conferences
Canadas, R.F., Cavalheiro, J.M.B.T., Guerreiro,
J.D.T., de Almeida, M.C.M.D., Pollet, E., Lobato da
Silva, C., da Fonseca, M.M.R., Ferreira, F.C.,
“Polyhydroxyalkanoates Fibrous Scaffolds for Sup-
port of Mesenchymal Stem cells”, 1st CLUSTER
Workshop in Materials and Nanotechnology, IST
Lisbon, December
Carvalho, F.D.R., Paradiso, P., Saramago, B., do
Rego, A.M.B., Fernandes, P., Towards a rational
approach for enzyme immobilization in a microreac-
tor framework, Portuguese Congress of Microbiolo-
gy and Biotechnology | Microbiotec’2013, Aveiro,
December.
Duarte, S., Rodrigues, L., Monteiro, G.,
“Heterologous production of curcumin by probiotic
lactic acid bacteria towards gastrointestinal cancer
therapy”, E3 Forum 2013, Lisbon, June
Duarte, S.O.D., Paulo, J., Machado, D., Rocha, I.,
Mergulhão, F.J.M., Rodrigues, L.R., Monteiro, G.A.,
“A synthetic biology approach to engineer
"therapeutic" bacteria”, Portuguese Congress of
Microbiology and Biotechnology | Microbiotec’2013,
Aveiro, December
Faria, N.T., Ferreira, C., Santos, M., Marques, S.,
Fonseca, C., Ferreira, F.C., “Sustainable glycolipids:
yeast conversion of lignocellulosic biomass into
mannosylerythritol lipids”, Portuguese Congress of
Microbiology and Biotechnology | Microbiotec’2013,
Aveiro, December
Magalhães, S., Duarte, S., Monteiro, G.A., Prieto,
M., Fernandes, F. “Trafficking studies of plasmid
DNA through Förster Resonance Energy Transfer”,
Portuguese Congress of Microbiology and Biotech-
nology | Microbiotec’2013, Aveiro, December
Magalhães, S., Nilsen, I.W., Monteiro, G.A.,
“Improvement of DNA vaccines”, E3 Forum 2013,
Lisbon, June
de Miguel, M., Ferreira, F.C., Baleizão, C., Farinha,
J.P., “Stimuli-Responsive Fiber Scaffolds for Stem
Cell Cultivation”, 1st CLUSTER Workshop in Materi-
als and Nanotechnology, Lisbon, December
Monteiro, M., Lourenço, N.M.T., Afonso, C.A.M.,
“Simple and more sustainable approaches for one
pot enzymatic resolution of sec-alcohols”, PC 87,
10th Portuguese National Meeting of Organic
Chemistry, Lisbon, September
Rocha, A., Lourenço, N.M.T., “Novel room-
temperature choline carboxylate zwitterionic ionic
liquids as potential electrolytes”, PC 1, 10th Portu-
guese National Meeting of Organic Chemistry, Lis-
bon, September
20 51 13 Annual Report
Rosa, A.M.M., Louro, A.F.D., Martins, S.A.M.,
Inácio, J.J., Azevedo, A.M., Prazeres, D.M.F.,
“Molecular Recognition of DNA Hybrids on Paper
Via the Anchoring of Antibodies With a Fusion of ZZ
-Domain With Carbohydrate-Binding Modules”, Por-
tuguese Congress of Microbiology and Biotechnolo-
gy | Microbiotec’2013, Aveiro, December
Šimčíková, M., Carreira, L., Gonçalves, G., Prather,
K.L.J., Prazeres, D.M.F., Monteiro, G.A., “The effect
of rpiA overexpression on plasmid biopharmaceuti-
cal production by Escherichia coli galg20, a pgi-
gene knockout strain”, Portuguese Congress of Mi-
crobiology and Biotechnology | Microbiotec’2013,
Aveiro, December
Simões, I.N., Vale, P., Soker, S., Atala, A., Cabral,
J.M.S., da Silva, C.L., Baptista, P.M., “Urinary
Rhabdosphincter Bioengineering – A Decellularized
Urethra Matrix for Modeling Stress Urinary Inconti-
nence In vitro and Tissue Engineering Applications”,
8th International Meeting of the Portuguese Society
for Stem Cells and Cell Therapies, Faro, May
Soares, R., Azevedo, A.M., Fernandes, P., Chu, V.,
Aires-Barros, M.R., Conde, J.P., “Integrated Extrac-
tion, Concentration and Quantification of Ochratoxin
A in Wines using a Microfluidic Aqueous Two Phase
Extraction coupled to a Fluorescence Linked Im-
munosorbent Assay”, Portuguese Congress of Mi-
crobiology and Biotechnology | Microbiotec’2013,
Aveiro, December
Szekely, Gy., Bandarra, J., Heggie, W., Sellergren,
B., Ferreira, F.C., “Scavenging Genotoxics from
Active Pharmaceutical Ingredients Streams by Mo-
lecular Imprinting and Nanofiltration”, 1st CLUSTER
Workshop in Materials and Nanotechnology, Lisbon,
December
Teixeira, R., Lourenço, N.M.T., “Synthesis of Novel
Task-Specific Ionic Liquids Bearing an Anhydride
Moiety”, PC 68, 10th Portuguese National Meeting
of Organic Chemistry, Lisbon, September
Trabuco, J.R.C., Martins, S.A.M., Monteiro, G.A.,
Chu, V., Conde, J.P., Prazeres, D.M.F., “Towards
the miniaturization of cell assays for GPCR monitor-
ing”, Portuguese Congress of Microbiology and Bio-
technology | Microbiotec’2013, Aveiro, December
Dissertations
Ph.D. Theses
Carlos Monteiro, PhD in Pharmaceutical and
Medicinal Chemistry, “Development of new synthet-
ic methodologies for organic synthesis based on
biocatalysis”, FF/UL (Supervisors: C.A.M. Afonso,
N.M.T. Lourenço)
Geisa Gonçalves, PhD in Bioengineering,
“Rational engineering of E. coli strains and vectors
for improved manufacturing of plasmid biopharma-
ceuticals”, IST/UL (Supervisors: D.M.F. Prazeres,
K.L.J. Prather, G.A. Monteiro)
João Cavalheiro, PhD in Biotechnology, “From
biodiesel glycerol to co- and ter- bacterial polyes-
ters”, IST/UL (Supervisors: M.M.R. Fonseca, M.C.M.
de Almeida)
Jonathan de la Vega, PhD in Biotechnology,
“Impact of plasmid downstream processing on tran-
sient transfection”, IST/UL (Supervisor: D.M.F.
Prazeres, G.A. Monteiro)
Michaela Simcíková, PhD in Bioengineering,
“Development of a process for the production and
purification of minicircles for biopharmaceutical ap-
plications”, IST/UL (Supervisor: G.A. Monteiro,
D.M.F. Prazeres)
Rimenys Jr Carvalho, PhD in Bioengineering,
“Phenylboronic Acid as Ligand for Multimodal Chro-
matography”, IST/UL (Supervisors: A.M. Azevedo,
S.M. Cramer, M.R. Aires-Barros)
Sezin Aday, PhD in Bioengineering, “Platforms to
modulate the activity of hematopoietic stem cells
and their progenies”, IST/UL (Supervisors: L. Fer-
reira, C. Lobato da Silva)
M.Sc. Theses
Alice Goudjil Portela, MSc in Biotechnology, “Ex-
vivo expansion of human Pluripotent Stem Cells
using alginate based culture systems, IST/UL
(Supervisors: F.C. Ferreira, J.M.S. Cabral)
Ana Filipa Pires, MSc in Bioenginneering,
“Assessing the use of conjugated polymers and
electric fields for cell culture”, IST/UL (Supervisors:
J. Morgado, F.C. Ferreira)
Ana Raquel Fortuna, MSc in Biological Engineer-
ing, “Early Breakthrough Detection during Chroma-
tographic Separation - a study directed to the mAbs
downstream process”, IST/UL (Supervisors: M. Ma-
teus, L. Villain)
Ana Teresa Bento, MSc in Biological Engineer-
ing, “Role of RET signals in human hematopoietic
stem cell transplantation, IST/UL (Supervisors: C.
Lobato da Silva, J.H. Veiga)
Ângelo Miguel Rocha, MSc in Química Farma-
cêutica e Terapêutica, “Desenvolvimento de meto-
dologias para síntese de fármacos metálicos e não-
metálicos, FF/UL, IST/UL (Supervisor: C.A.M. Afon-
so, N.M.T. Lourenço)
Antonio Lima Grilo, MSc in Biological Engineer-
ing, “Aqueous Two-Phase Systems for Large Scale
Purification of Monoclonal Antibodies”, IST/UL
(Supervisors: A.M. Azevedo, G. Vedantham)
André Nascimento, MSc in Biotechnology,
“Polishing of Monoclonal Antibodies Stream through
Convective Flow Devices, IST/UL (Supervisors:
A.M. Azevedo, M. Mateus)
André Fernandes, MSc in Biological Engineer-
ing, “Ozonation or evaporation as a wastewater
treatment after aneorobic methanization for its recir-
culation to bioethanol production process”, IST/UL
(Supervisors: D.M.F. Prazeres, M. Kamiński)
Bárbara Silva, MSc in Biological Engineering,
“New sparse modelling tools in flavour research”,
IST/UL (Supervisors: J.M.C. Menezes, R. Bro)
Bernardo Abecasis, MSc in Biological Engineer-
ing, “Developing an Advanced Therapy Medicinal
Product (ATMP) for regulatory approval: optimiza-
tion of product release and shelf life”, IST/UL
(Supervisors: C. Lobato da Silva, F. Santos)
Bruno Santos Raquel, MSc in Biological Engine-
ering, “Desenvolvimento de uma metodologia de
avaliação de riscos para planeamento de activida-
des de manutenção numa indústria farmacêutica”,
IST/UL (Supervisors: M.C. Fernandes, L.P. Fonse-
ca)
Catarina Marciano Alves, MSc in Biological Engi-
neering, “Evaluation of alternative feedstocks for
succinic acid production”, IST/UL (Supervisors:
J.A.L Santos, M. Jansen)
Catarina Sanches Seita, MSc in Biological Engi-
neering, “Flexible Modular Process Design for Enzy-
matic Biodiesel Production”, IST/UL (Supervisors:
L.P. Fonseca, J.M. Woodley)
Cristiana Pardal, MSc in Pharmaceutical Engine-
ering, “Otimização do processo de produção de
uma formulação de comprimidos revestidos”, IST/
UL (Supervisors: J.M.C. Menezes, P. Salústio)
Daniel Pais, MSc in Biological Engineering,
“Towards a Microfluidic Chemoenzymatic Reactor”,
IST/UL (Supervisors: D.M.F. Prazeres, N. Szita)
Diana Santos, MSc in Biomedical Engineering,
“Culture Platform for Induction of Human Induced
Pluripotent Stem Cells into Cortical Neural Stem and
Progenitor Cells under Chemically Defined Condi-
tions”, IST/UL (Supervisors: M.M. Diogo, J.M.S. Ca-
bral)
Diogo Valente, MSc in Biological Engineering,
“cGMP activities in the context of a Contract Manu-
facturing Organization (CMO)”, IST/UL (Supervisors:
D.M.F. Prazeres, R. Fortunato)
Diogo Sebastião, MSc in Biological Engineering,
“Photosynthetic algal microbial fuel cell: Bacteria
and microalgae as biocatalysts for energy produc-
tion and byproducts valorization”, IST/UL
(Supervisors: F.C. Ferreira, C. Matos)
Diogo de Sousa Pinto, MSc in Biotechnology,
“Maximizing human mesenchymal stem/stromal
cells therapeutic potential through 3-D cell cultiva-
tion, IST/UL (Supervisors: C. Lobato da Silva,
J.M.S. Cabral)
Fábio Lampreia, MSc in Biotechnology,
“Overexpressing BDNF in Neural Stem Cells using
non-viral gene delivery strategies, FCT/UNL
(Supervisor: C. Madeira)
Inês Ferreira, MSc in Bioenginneering,
“Biofunctionalization of electrospun poly(epslon-
caprolactone) nanofibers to promote neural stem
cell adhesion, alignment and expansion”, IST/UL
(Supervisors: F.C. Ferreira, M.M. Diogo)
Inês Nunes, MSc in Pharmaceutical Engineering,
“Formulation and Analytical Methods Development
of Feminine Hygiene Specific Products”, IST/UL
(Supervisors: J.M.C. Menezes, H. Marques)
Inês Fernandes Pinto, MSc in Biological Engi-
neering, “Novel capture processes for monoclonal
antibodies purification”, IST/UL (Supervisors: A.M.
Azevedo, M.R. Aires Barros)
Inês Filipa Louro, MSc in Biological Engineer-
ing, “Mesenchymal stem/stromal cells: comparative
study in four cell types on their expandability in cul-
ture and on their safety profiles”, IST/UL
(Supervisors: C. Lobato da Silva, H. Cruz)
Joana Cecilio, MSc in Pharmaceutical Enginee-
ring, “Desenvolvimento de Métodos de Espectrosco-
pia de Infravermelho Próximo com Aplicação na
Industria Farmacêutica”, IST/UL (Supervisors:
J.M.C. Menezes, S. Rosa)
Inês Clemente, MSc in Biological Engineering,
“Encapsulation of Lactobacillus casei and its stability
in model foods”, IST/UL (Supervisors: M. Mateus, S.
Horáčková)
Joana Faustino, MSc in Biological Engineering,
“Off-line Dynamic Image Analysis vs PAT Monitoring
Tools on a Lab-Scale Hot Melt Coating Process”,
IST/UL (Supervisors: J.M.C. Menezes, S. Sacher)
20 53 13 Annual Report
Joana Carmelo, MSc in Biological Engineering,
“Optimizing the production of human mesenchymal
stem/stromal cells in xeno-free microcarrier-based
reactor systems”, IST/UL (Supervisors: C. Lobato
da Silva, J.M.S. Cabral)
Joana da Silva, MSc in Biological Engineering,
“Characterization and modulation of central nervous
system immune response following transplantation
of mesenchymal stem cells into the mouse brain,
IST/UL (Supervisors: C. Lobato da Silva, P.
Ponsaerts)
Joana Galante, MSc in Biological Engineering,
“Vegetable Protein Functionality. From Milk Ana-
logue to Fiber”, IST/UL (Supervisors: M. Mateus, F.
van de Velde)
João Carlos da Silva, MSc in Biomedical Engi-
neering, “Genetic engineering of synovial-derived
mesenchymal stem cells for cartilage regeneration,
IST/UL (Supervisors: C. Madeira, J.M.S. Cabral)
João Belchior, MSc in Biotechnology, “Screening
and evaluation of synthetic protein-mimic affinity
ligands for the purification of plasmid DNA, IST/UL
(Supervisors: M.A. Taipa, D.M.F. Prazeres)
João Crispim, MSc in Biological Engineering,
“High throughput screening platform for embryonic
development in vitro”, IST/UL (Supervisors: C. Lo-
bato da Silva, E. Vrij)
João Monteiro, MSc in Biotechnology,
“Establishment of a novel process for the purifica-
tion of cutinase with triazine-scaffolded synthetic
affinity ligands, IST/UL (Supervisor: M.A. Taipa)
Leonor Serra, MSc in Biological Engineering,
“Simultaneous Saccharification and Fermentation
for the Production of Itaconic Acid with Ustilago
maydis, IST/UL (Supervisors: J.A.L. Santos, D.
Kreyenschulte)
Liliana Agostinho, MSc in Biomedical Engineer-
ing, “Strategies for optimization of ex-vivo expansion
of human hematopoietic stem/progenitor cells from
the umbilical cord blood”, IST/UL (Supervisors: C.
Lobato da Silva, J.M.S. Cabral)
Luana Cardoso Grangeiro, MSc in Biotechnolo-
gy, “Preparation, characterization and performance
of chromatographic membrane with phenylboronate
ligands for biomolecules purification, IST/UL
(Supervisors: M. Mateus, A.M. Azevedo)
Luís Carreira, MSc in Biotechnology, “Evaluation of
rpiA promoter strength in plasmid DNA production”,
IST/UL (Supervisor: G.A. Monteiro)
Luís Carreira, MSc in Biological Engineering,
“Handling complex GC-MS-based metabolomics
data: A uni- and multivariate statistical analysis ap-
proach”, IST/UL (Supervisors: J.M.C. Menezes, R.
Duarte)
Mafalda dos Santos, MSc in Biological Enginee-
ring, “Implementação de normas específicas para o
desenvolvimento e produção de dispositivos médi-
cos e o seu impacto qualitativo nas atividades de
IDI num contexto de "start-up" tecnológica”, IST/UL
(Supervisors: D.M.F. Prazeres, A. Soares)
Marcelo da Silva, MSc in Biological Engineering,
“Advanced numerical techniques for optimal experi-
mental design applied to microbial kinetics”, IST/UL
(Supervisors: A.M. Azevedo, J. Van Impe)
Márcia Antunes, MSc in Biological Engineering,
“Production of recombinant human xanthine oxidase
in E. coli and optimization of its application for pre-
parative synthesis of oxidized drug metabolites, IST/
UL (Supervisors: A.M. Azevedo, M. Kittelmann)
Margarida Braga, MSc in Biological Engineering,
“Análise instrumental da textura em produtos de
panificação”, IST/UL (Supervisors: M. Mateus, M.
Esquível)
Margarida Azevedo, MSc in Biotechnology,
“Improvement of avian influenza DNA vaccine can-
didates: The impact of antigen-targeting sequences,
IST/UL (Supervisors: G.A. Monteiro, M. Fevereiro)
Maria Gonçalves Fernandes, MSc in Biological
Engineering, “Study of autophagy in Tauopathies,
IST/UL (Supervisors: F.C. Ferreira, H. Vieira)
Maria João Sebastião, MSc in Biotechnology,
“Expansion of human Neural Stem Cells in micro-
carrier-based spinner flask culture systems, IST/UL
(Supervisors: M.M. Diogo, C.A.V. Rodrigues
Marilena Ornelas, MSc in Biological Engineer-
ing, “Aggregation behaviour of globular proteins”,
IST/UL (Supervisors: M. Mateus, F. Van de Velde)
Marta dos Santos Matias, MSc in Biological En-
gineering, “Estratégias de Melhoria Contínua de
Processos: Monitorização e Optimização em Linhas
de Produção Alimentar”, IST/UL (Supervisors: M.
Mateus, C. Faustino)
Miguel Luís Ribeiro, MSc in Pharmaceutical En-
gineering, “Implementation of an anti-counterfeiting
device - enhancing supply chain robustness by a
Risk management approach”, IST/UL (Supervisors:
J.M.C. Menezes, J. Moreira)
Mónica Inês Peralta, MSc in Biological Enginee-
ring, “Validação de Sistemas informatizados”, IST/
UL (Supervisors: L.P. Fonseca, D. Silva)
Olga Sofia Reis, MSc in Pharmaceutical Engi-
neering, “Evaluation of a Fluidized Bed Wet Granu-
lation Process using a QbD approach”, IST/UL
(Supervisors: J.M.C. Menezes, J. Abreu Pinto)
PedroSilva, MSc in Biomedical Engineering,
“Purification of Human Induced Pluripotent Stem
Cell-Derived Cells for Regenerative Medicine Appli-
cations”, IST/UL (Supervisors: M.M. Diogo, J.M.S.
Cabral)
Pedro Pereira, MSc in Biological Engineering,
“Biomimetic replicas - Transfer of complex architec-
tures from plant surfaces onto polymeric materials”,
IST/UL (Supervisors: D.M.F. Prazeres, G.A. Mon-
teiro)
Pedro Couto, MSc in Biological Engineering,
“Comparative Analysis of Two Different Isolation
and Cryopreservation protocols of Human Mesen-
chymal Stem/Stromal Cells from the Umbilical Cord
Matrix”, IST/UL (Supervisors: C. Lobato da Silva, C.
Cardoso)
Raquel Santos, MSc in Biotechnology, “An alterna-
tive capture step for monoclonal antibodies: phenyl-
boronate as a new multi-modal ligand”, IST/UL
(Supervisors: A.M. Azevedo, M.R. Aires Barros)
Rita Pais, MSc in Biological Engineering, “Estudo
da complexação do limoneno com ciclodextrinas
estruturalmente diferentes”, IST/UL (Supervisors: M.
Mateus, C.M.M. Duarte)
Rúben Soares, MSc in Biotechnology, “Integrated
Extraction, Concentration and Quantification of
Ochratoxin A in Wines using a Microfluidic Aqueous
Two Phase Extraction coupled to a Fluorescence
Linked Immunosorbent Assay, IST/UL (Supervisors:
M.R. Aires Barros, J.P Conde)
Sandra Bernardo, MSc in Biotechnology,
“LYTAG-driven Integrative Platform for Purification
of Monoclonal Antibodies by Aqueous Two-phase
Systems, IST/UL (Supervisors: M.R. Aires Barros,
A.M. Azevedo)
Sandra Margarido, MSc in Biological Enginee-
ring, “Implementação de uma metodologia de análi-
se sensorial no plano de controlo de qualidade dos
xaropes de glucose-frutose”, IST/UL (Supervisors:
J.A.L. Santos, M.R. Oliveira)
Sara Cardoso, MSc in Biological Engineering,
“Testing of CIM™ monolithic chromatographic sup-
ports for plasmid DNA purification, IST/UL
(Supervisors: D.M.F. Prazeres, U. Černigoj)
Susana Santos, MSc in Biological Engineering,
“Growth and cell cycle kinetics of AML and CLL cell
lines in a 3D bone marrow biomimicry under oxida-
tive and starvation stresses”, IST/UL (Supervisors:
F.C. Ferreira, A. Mantalaris)
Tânia Baltazar, MSc in Biotechnology,
“Monolayer Differentiation of Human Induced Plu-
ripotent Stem Cells (hiPSC) into Cardiomyocytes,
IST/UL (Supervisors: M.M. Diogo, J.M.S. Cabral)
Tatiana Sirgado, MSc in Biomedical Engineering,
“Human Mesenchymal stem cells cultivation on nat-
ural/synthetic polymeric supports, IST/UL
(Supervisors: F.C. Ferreira, C. Lobato da Silva)
Teresa Pereira, MSc in Biological Engineering,
“Non-viral engineered human mesenchymal stem/
stromal cells to promote angiogenesis”, IST/UL
(Supervisors: C. Lobato da Silva, G.A. Monteiro)
Tiago Ferro, MSc in Biomedical Engineering and
Biophysics, “Isolation, characterization and ex-vivo
expansion of human synovial tissue derived-
mesenchymal stem/stromal cells”, FC/UL
(Supervisors: J.M.S. Cabral, Hugo Ferreira (FC/UL))
Tiago Pinto, MSc in Biological Engineering,
“Production of biohydrogen through the fermentation
of Spirogyra sp. biomass by Clostridium butyricum,
IST/UL (Supervisors: C.C.C.R. de Carvalho, P. Silva
Moura)
Vanessa Silva, MSc in Biological Engineering,
“Fed-batch production of FAME-biodiesel from rape-
seed oil catalysed by a liquid lipase formulation –
optimizing process parameters to maximize catalyst
productivity”, IST/UL (Supervisors: L.P. Fonseca,
J.M. Woodley)
Vasco Silva, MSc in Biotechnology, “Preparation
and characterization of chitosan nanoparticles for
gene delivery, IST/UL (Supervisor: M. Mateus)
Vera André, MSc in Biological Engineering,
“Monitorização e Controlo da Segurança Alimentar
na Produção Industrial de Snacks”, IST/UL
(Supervisors: M. Mateus, A. Parreira)
20 55 13 Annual Report
Staff Faculty
Joaquim M.S. Cabral
Maria Raquel Aires-Barros
Duarte Miguel Prazeres
Luís Fonseca
José Menezes
Cláudia Lobato da Silva
Gabriel Monteiro
José Santos
Maria Ângela Taipa
M. Margarida Diogo
Marília Mateus
Research Scientists
Carla C.C.R. de Carvalho
Frederico Ferreira
Ana Azevedo
Pedro Fernandes
Teresa Catarina Madeira
Post-doctoral Fellows
Ana Fernandes-Platzgummer
Carlos Rodrigues
Dragana de Barros
Marisa Salgueiro
Nuno Lourenço
Sara Badenes
Sofia Martins
Sudarsu Ramanaiah
Tiago Fernandes
PhD Students
Alexandra Hertrampf
Ana Rosa
António Soure
Aruna Santhagunam
Cláudia Miranda
Daniel Camarneiro Silva
Filipe Carvalho
Francisco Moreira
Geisa Gonçalves
Gonçalo Rodrigues
Inês Fernandes Pinto
Irina Simões
Javad Hatami
Joana Boura
João Guerreiro
João Trabuco
Jonhathan de la Vega
Jorge Pascoal
Luís Raiado Pereira
Lúcia Volta e Sousa
Márcia Mata
Marisa Santos
Marta Costa
Michaela Simcikova
Miriam Sousa
Nuno Faria
Rimenys Carvalho
Rui Carvalho
Salomé Magalhães
Sofia Duarte
Tiago Dias
Tomás Dias
Master Students
Alice Portela
André Nascimento
Carlos Rodrigues
Cátia Jorge
Diana Marques
Diana Santos
Dina Antunes
Diogo Pinto
Fábio Gonçalves
Fábio Lampreia
Inês Ferreira
Inês Pimentel
Isabel Pinto
João Belchior
João Monteiro
João Silva
Liliana Agostinho
Liliana Brito
Luana Grangeiro
Luis Carreira
Margarida Azevedo
Maria João Sebastião
Mariana Pina
Raquel Santos
Rita Fernandes
Samuel Jorge
Sandra Bernardo
Sara Mateus
Tânia Baltazar
Tatiana Sirgado
Teresa Trindade
Tiago Ferro
Vasco Silva
Research Assistants
Andreia Fernandes
Fátima Cristina Pinto
Joana Carmelo
Joana Serra
Jorge Paulo
Maria João Jacinto
Marina Monteiro
Pedro Prereira
Ruben Soares
Sara Matias
Sara Rosa
Technician
Ricardo Pereira
BERG
BioEngineering Research Group
Institute for Biotechnology and Bioengineering
Instituto Superior Técnico
Av. Rovisco Pais
1049-001 Lisbon
Portugal
www.ibb.pt/berg