nanomedicine_(1)

Medical Devices

RESEARCH

DEPARTMENTS
Lifescience
NANOHEALTH
RESEARCH GROUPS
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DESCRIPTION

The research of the Medical Devices group is focused on the development of technologies for the understanding and diagnosis of diseases. MD works in close collaboration with the clinic to enable translational medical research towards the realisation of precision medicine. To this aim, MD works in the development of new optical instrumentation, microfluidic devices, biosensors and biomimetic systems to study and evaluate disease biomarkers, distributed in 3 different research lines:

1- Biomicrofluidic systems for the isolation of tumor-derived material from body fluids, nanobiosensors for the multiplex characterization of cancer biomarkers, and their integration in organ-on-a-chip 3D models. Lead by Lorena Diéguez.

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2- Development of optical technology contributing to answer outstanding questions in the life sciences. Lead by Pieter de Beule.

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ON GOING RESEARCH PROJECTS

Combined Microscopies

The widespread availability of a variety of medical imaging technologies has constituted one of the driving forces behind the revolution in medical diagnosis over the last century. As of today, disease diagnosis often results from a combination of medical examinations that present a multiplexed view of the patient’s medical condition to the medical doctor. Similarly, the development of new medical treatment procedures has benefitted and will profit greatly from the widespread availability of new advances in microscopy that provide crucial new insights into human cell biology. These advances are spread over the realms of optical, electron and Scanning Probe Microscopy (SPM).

The Applied Nano-Optics Laboratory team has developed a new variant of combined microscopy, based on a fluorescence optical sectioning microscopy module and atomic force microscopy (AFM), a well-known variant of SPM.[1] By creating a time independent fluorescence excitation light illumination of the AFM cantilever, we enable for the first time the simultaneous recording of fluorescence optically sectioned images and various AFM recording modes. We envision that this development will have a significant impact in the study of live-cell signalling processing in cellular biology and are currently exploring this with the team of Prof. Sandra Paiva at the University of Minho.

Combined microscopies

  1. Miranda A, Martins M, De Beule PAA. Simultaneous differential spinning disk fluorescence optical sectioning microscopy and nanomechanical mapping atomic force microscopy. Rev Sci Instrum. 2015; 86(9):093705.
  2. Miranda A, Martins M, De Beule PAA. Simultaneous Advanced Microscopies for Live Cell Signaling Dynamics Investigations. Biophys J. 2016;110(3):517a.
  3. Rosana Alves, Daphné Dambournet, Alexander Sorkin, Adelaide Miranda, Pieter A. A. De Beule, David Drubin and Sandra Paiva. Characterization of intracellular trafficking of nutrient transporters using combined fluorescence optical sectioning and nanomechanical mapping atomic force microscopy in mammalian cells. XIX. Annual Linz Winter Workshop. 3-6th February 2017. Advances in Single-Molecule Research for Biology & Nanoscience, Linz, Austria.

INL researchers: Pieter De Beule, Marco Martins & Adelaide Miranda

Scientific Visitors: Sandra Paiva, Rosana Alves, Claudia Barata Antunes

Optical Scattering and Imaging of Cellular Exo- and Endocytosis

Endocytosis, the taking in of matter by a living cell by invagination of its membrane to form a vacuole, and exocytosis, the process of vesicles budding off membranes for the transport of membrane bound secretory vesicles to the extracellular matrix, exemplify fundamental processes in biology. In-vivo detection of both exo- and endocytosis currently represents a formidable challenge to image capture technology due to the speed of the event, the size of the lipid vesicles and optical contrast available.

This project aims to introduce an exact electromagnetic theoretical model for the quantitative understanding of how exo- and endocytosis is observed with video Differential Interference Contrast (DIC) microscopy. [1] In particular, it focuses on the fundamental understanding of how lipid-induced optical anisotropy influences the microscopic observation of exo- or endocytosis. For this project we gratefully acknowledge aid received through the SCATMECH polarized light scattering software library developed by Dr. Thomas A. Germer at NIST.[2]

Optical Scattering

  1. De Beule PAA. Surface scattering of core–shell particles with anisotropic shell. J Opt Soc Am A. 2014; 31(1):162.
  2. SCATMECH Project Home Page
  3. Dylan Marques, Adelaide Miranda, Ana G. Silva, Pieter A. A. De Beule. Optical scattering of cellular exo- and endocytosis. XIX. Annual Linz Winter Workshop. 3-6th February 2017, Advances in Single-Molecule Research for Biology & Nanoscience, Linz, Austria.

INL researchers: Adelaide Miranda, Pieter De Beule

Scientific visitor: Dylan Marques, Ana Silva

Advanced Ellipsometry

Thin film fabrication and characterization forms one of the cornerstones of modern nanotechnology. Optical models of these thin films often require more complexity than an isotropic model in order to describe device application. At INL we have introduced a new variant of spectroscopic imaging ellipsometer that delivers improved thin film anisotropy measurements on a microscopic scale with strongly improved performance at the solid-liquid interface.[1] We have applied this system for the spatially resolved determination of lipid bilayer optical anisotropy and are currently exploring applications for the characterization of exotic new 2D materials including di- and trichalcogenides

We have also introduced advanced ellipsometry for the detection of protein adhesion to nanoparticles deposited on a substrate. Thereby, we propose ellipsometry as an alternative to standard Surface Plasmon Resonance detection platforms for monitoring protein surface adhesion.[2]

Advanced Ellipsometry

  1. Miranda A, De Beule PAA. Microscopic thin film optical anisotropy imaging at the solid-liquid interface. Rev Sci Instrum. 2016;87(4):043701
  2. Viegas D, Fernandes E, Queirós R, Petrovykh DY and De Beule PAA. Adapting Bobbert-Vlieger model to spectroscopic ellipsometry of gold nanoparticles with bio-organic shells. Biomed. Opt. Express 8, 3538-3550 (2017)

INL researchers: Pieter De Beule, Adelaide Miranda

NanoTRAINforGrowth II

NANOTRAIN_LOGOThe Cofund project

Microfluidics and plasmonics join efforts on the hunt for a platform that can help oncologists in cancer prognosis. The COFUND project led by Dr Sara Abalde-Cela in collaboration with Dr Lorena Diéguez relays on nanotechnology and microfluidics to develop a real-time, high-throughput and multiplex cancer-sensing platform. A major advance recently achieved by INL researchers is a microfluidic platform able to isolate the very rare cancer cells present in the blood of metastatic patients, the so-called circulating tumour cells (CTCs).  These CTCs are a snapshot of the current cancer status of each patient, that hold predictive and prognostic value. However, after isolation of CTCs, many challenges remain ahead to fully unravel cancer behaviour and evolution. In order to extract as many information as possible from those cells, very advanced interrogating techniques need to be applied. In this context, Surface-enhanced Raman scattering (SERS) spectroscopy arises as the ideal analytical technique due to its inherent sensitivity, specificity, multiplexing and quantification abilities. Thus, SERS plus microfluidics is a powerful combination able to overcome the current bottlenecks faced by researchers within the liquid biopsy field.

Several lines of research are being pursued by researchers involved within this project including: the synthesis of codified gold nanostars for the indirect analysis of extra and intra-cellular biomarkers; the encapsulation of the isolated CTCs in microdroplets acting as microreactors for single-cell analysis and metabolite single-cell tracking; and single-cell evolution for predicting tumour growth. Even though this project has been running at INL for less than a year, the proof-of-concept with cell lines has already started, and optimisation of plasmonic nanoparticles has been completed at this stage. Results and project concept have been spread to the community at several conferences and scientific events in Portugal, Spain, UK, Japan and Sweden. The feedback from the scientific community has been very positive so far, including some conference awards. Our preliminary results, the support from INL and research community, together with the hope that we can contribute to the cancer fight, encourage us to give our best to this challenging, but exciting project.

INL researcher: Sara Abalde

CANCER – ADVANCING CANCER RESEARCH: FROM BASIC KNOWLEDGE TO APPLICATION

barra_assinaturasThe mission of the CANCER structured Program is to create a platform of integrated competences that promotes translation of basic research to clinical application in the area of oncology. The strategy for development of this program relies on building a conceptual scientific and technologic platform, where integration between basic and applied research is fostered. The CANCER Program will also rely on our well-established collaborations with the pharmaceutical and in vitro diagnostics industry to boost the likelihood of creating economic value, hence complying with the smart specialization RIS3 strategy for Norte Portugal. Numerous researchers from four institutions Ipatimup/i3S, IBMC/i3S, INL and CINTESIS under the co-ordination of Ipatimup/i3S, are involved in this program with five research lines in co-promotion:
1- Novel therapeutic targets and models for cancer;
2- Dynamics of intra-tumor heterogeneity;
3- Determinants of cell invasion and metastization in cancer;
4- Innovative biomarkers for cancer diagnosis, prognosis and therapy optimization;
5- Microsystem platforms for early cancer diagnosis & disease progression monitoring.

Several lines of research are being pursued by researchers involved within this project including: the synthesis of codified gold nanostars for the indirect analysis of extra and intra-cellular biomarkers; the encapsulation of the isolated CTCs in microdroplets acting as microreactors for single-cell analysis and metabolite single-cell tracking; and single-cell evolution for predicting tumour growth. Even though this project has been running at INL for less than a year, the proof-of-concept with cell lines has already started, and optimisation of plasmonic nanoparticles has been completed at this stage. Results and project concept have been spread to the community at several conferences and scientific events in Portugal, Spain, UK, Japan and Sweden. The feedback from the scientific community has been very positive so far, including some conference awards. Our preliminary results, the support from INL and research community, together with the hope that we can contribute to the cancer fight, encourage us to give our best to this challenging, but exciting project.

INL researchers: Lorena Diéguez, Lei Wu

FROnTHERA: FROntiers of technology for THERAnostics of cancer, metabolic and neurodegenerative diseases

barra_assinaturasThe main of objective of FROnTHERA is to boost the progress of Tissue Engineering and Regenerative Medicine fields with main focus on cancer, diabetes and neurodegenerative diseases. To accomplish this, the merge of 3D tissue engineered in vitro models of diseases, microfluidics, nanotechnologies, molecular biology and embedded biosensors will be pursued in order to obtain new tools and technologies to be used as alternative to animal experimentation, as well as, personalized therapies for Human health. Ultimately, the strengthening of these interdisciplinary domains will allow the improvement of theranostics of RIS3 diseases. This project is an initiative of three top leading research units, located in the PT 11 region, and gathers experts in tissue engineering in vitro models, neurosciences and emergent technologies based on responsive biosensors, whose main goal is to dvance in research for developing tools and technologies to be used as alternative to animal experimentation and in personalised therapies for human health.

INL researchers: Lorena Diéguez, Krishna Kant

SAM – Simultaneous Advanced Microscopies

FCT_LOGO-768x257The project will focus on the study of AFM cantilver bending upon excitation with fluorescence light; generating recommendations for designing optimal AFM cantilevers for combined fluorescence – AFM microscopy, and determining heating induced by AFM cantilevers excited by excitation light. The project aims to develop a system combining Structured Illumination Microscopy with Atomic Force Microscopy and apply it to cellular biology questions.

The main goal of the SAM Project is to develop new technology that combines Atomic Force Microscopy in liquid and superresolution fluorescence microscopy and enable simultaneous data acquisition. This new technology will be applied to the investigation of cellular nutrient and metal transporters.

 

People at the project:

INL: Pieter De Beule & Catarina Moura.

IMPAct-L – Innovative Microfluidic Platform for Analysis of myeloid Leukemia blasts

bar-logoAcute myeloid leukemia (AML) is the most common form of acute leukemia in adults that, although having favourable outcomes for younger patients upon receiving treatment, has a very poor prognosis in the elderly. After treatment with chemotheraphy, even patients that clinically achieve Complete Remission (CR) can relapse through the persistence of Minimal Residual Disease (MRD), having fatal consequences. The low sensitivity of current diagnostic technologies based on flow cytometry and bone marrow biopsy often prevents early detection of MRD, while being highly invasive and costly. Accurate and early diagnosis of MRD would allow the application of appropriate theraphy, improving dramatically the prognosis of the patients. Thus, the scope of this project is to discover new biomarkers of AML through Next Generation Sequencing, and to design, fabricate, test and optimize new Lab-on-a-chip systems based on Surface Enhanced Raman Scattering and microfluidics for early detection of MRD in AML.

Main Goal:

The project aims at developing an innovative in vitro diagnostic system based on Key Enabling Technologies for early detection of Minimal Residual Disease in Acute Myeloid Leukemia.

INL researcher: Lorena Diéguez, Sara Abalde-Cela & Alexandra Teixeira.

Nanotechnology based functional solutions

barra_assinaturasThe major goals set for the integrated project cover an increase of our human resources in strategic areas by hiring 15 new researchers for the 2 research lines, a strengthening of our core activities in various project areas (sensing, system integration etc.) as well as the opening of new scientific topics (thermal energy harvesting, label free optical/graphene biosensors, etc.), and re-enforcing partnerships and collaborations with major national/regional industrial actors (electronics, health, food and environment, materials ).

Line 1-Nanotechnology based autonomous sensing systems – (energy harvesting and storage, sensors, new materials and concepts, systems integration towards IOT)

Line 2-Nanotechnology enabled solutions for water, food, and health challenges – (Water monitoring and treatment, food quality and safety, food processing and subproduct valorization, nano in diagnostics, nano in therapeutics)

The program will provide nanotechnology-based solutions for 2 areas: autonomous sensing systems (targeting Internet-of-Things integration) and monitoring and treatment platforms for applications related to water, food, and health. Each challenge is the focus of a research line, while the program integrates both lines at several levels via shared and reciprocal goals, new technology platforms and (nano)materials, and characterization methods.

INL researchers: Pieter De Beule, Adelaide Miranda & Mariana Carvalho.

GROUP LEADER

Lorena Dieguez - 1_w

THE TEAM

Staff Researchers:

Pieter de Beule

Research Fellows:

Catarina Moura
Sara Abalde-Cela
Lei Wu
Krishna Kant

Research Engineers:

Adelaide Miranda

Scientific Associates:

Aline Marie Fernandes
Ana Gómez
Alexandra Teixeira
Paulina Piairo

Ph.D Students:

Cláudia Barata
Rosana Alves

MSc Students:

Rita Natividade
Cláudia Lópes
Kevin Oliveira
Pedro Conceição
José Maria Fernandes
Beatriz Patrocinio

 

Former Members

Marina Brito
Staff Researcher (2018)

Daniel Stähli
MSc Student (2018)

Silvina Samy
Ph.D. Student (2017)

João Fernandes
MSc Student (2017)

QUANTUM-PTI_Social-media_v2Apply with us for a Quantum position as PhD student and Join our Team!

“Quantum Imaging for the Life Sciences”

if you are interested on this topic or if you have any doubt/other suggestions please contact by email to Dr. Pieter De Beule.

Research Area: Quantum Sensing

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RESEARCH

DEPARTMENTS
Lifescience
NANOHEALTH
RESEARCH GROUPS
BUTTON-nanomedicine
BUTTON-medical-devices