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.
2- Development of optical technology contributing to answer outstanding questions in the life sciences. Lead by Pieter de Beule.
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. 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.
- 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.
- Miranda A, Martins M, De Beule PAA. Simultaneous Advanced Microscopies for Live Cell Signaling Dynamics Investigations. Biophys J. 2016;110(3):517a.
- 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.
People at the project:
INL: 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.  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.
- De Beule PAA. Surface scattering of core–shell particles with anisotropic shell. J Opt Soc Am A. 2014; 31(1):162.
- SCATMECH Project Home Page
- 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.
People at the project:
INL: Adelaide Miranda, Pieter De Beule
Scientific visitor: Dylan Marques, Ana Silva
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. 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.
- Miranda A, De Beule PAA. Microscopic thin film optical anisotropy imaging at the solid-liquid interface. Rev Sci Instrum. 2016;87(4):043701
- 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)
People at the project:
INL: Pieter De Beule, Adelaide Miranda
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.
People at the project:
INL: Sara Abalde
José Maria Fernandes
Staff Researcher (2018)
MSc Student (2018)
Ph.D. Student (2017)
MSc Student (2017)