The BioSciences Screening scientific platform provides state-of-the-art instruments and competence to solve challenging biological questions with high throughput and high content technologies. Highly qualified scientists with expertise on project evaluation, assay development, liquid handling, automated microscopy, multimode microplate readers, image and data analysis, work with project teams to successfully plan, develop, run and analyze screens. Examples are the development of genetic and chemical screening campaigns with advanced human cell-based models. The platform facilitates access to genetic and small-molecule screening libraries aiming for the discovery of new chemical and biological entities with potential therapeutic applications.

The BioSciences Screening platform participates and coordinates the PT-OPENSCREEN, a countrywide network of chemistry and biology institutes that conduct compound synthesis, as well as cell and biochemical assays for screening, optimizing compounds, and carrying out follow-up activity studies. In addition, it serves as a partner site for EU-OPENSCREEN, a European Research Infrastructure Consortium for chemical biology and early drug discovery, and participates in the Portuguese Platform of BioImaging (PPBI) as well as various COST actions.

Click here for a virtual tour of the scientific platform. 

First time users need to contact the platform staff to get training and access to equipment booking.

Three access modes are provided:

1. Equipment usage only

• Upon training, users can book and use the equipment at their own convenience. For some equipment restrictions may apply.
• Please read below the general user policy. 
• All reagents/consumables must be purchased by the user. The platform can provide several reagents/consumables as part of the service. Check list here.
• See here the available equipment.
• See here equipment usage fees.

        2. Project development mode

• The platform can deliver a more integrative and collaborative approach by providing consultancy during project writing, project evaluation, assay development and validation, pilot-screening; prior to project submission.
• For project implementation, the platform will train the project team to use the laboratory facilities, automation and screening, perform data acquisition, image and data analysis.
• All reagents/consumables must be purchased by the user. The platform can provide several reagents/consumables as part of the service. Check list here.
• Same fees apply as in Equipment usage only.

        3. Service request mode

• The platform can deliver a complete approach by providing, project evaluation, project development, assay development and validation, laboratory facilities, automation and screening, automated microscopy, image and data analysis, reporting.
• All reagents/consumables and human resources will be provided by the platform.
• Costs are evaluated upon service request.

 

Acknowledegments to the Scientific Platform

In compliance with the i3S Scientific Platforms Acknowledgments approved in C.E. 17/07/2017: 

Whenever you use resources (equipment or technical support) from i3S Scientific Platforms you should acknowledge their contribution always referring “i3S Scientific Platform”.

If members of the i3S Scientific Platforms also provided significant intellectual contribution to the study, “i3S Authorship guidelines” apply.

 

As the BioSciences Screening Scientific Platform belongs to the Portuguese Roadmap of Research Infrastructures (FCT) your acknowledegement should also refer that.  Please use one of the following sentences or similar:

 

Example 1: The authors acknowledge the support of the i3S Scientific Platform BioSciences Screening [and other scientific Platforms, if applies], member of the national infrastructures PT-OPENSCREEN (NORTE-01-0145-FEDER-085468) and PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122).

Example 2: The authors acknowledge the support of the i3S Scientific Platform BioSciences Screening [and other scientific Platforms, if applies], member of the PT-OPENSCREEN (NORTE-01-0145-FEDER-085468) and PPBI (PPBI-POCI-01-0145-FEDER-022122).

Example 3: YY technique was performed at the BioSciences Screening i3S Scientific Platform (member of the PT-OPENSCREEN (NORTE-01-0145-FEDER-085468) and PPBI (PPBI-POCI-01-0145-FEDER-022122)) with the assistance of..."

 

Please also send us a copy or the reference of the published work (article, thesis, other,...).

The Biosciences Screening scientific platform has 3 main areas of activity: 

1. High Throughput and/or High Content Screening
2. Bioimage data analysis
3. Stand-alone usage of equipment

 

 

BioSciences Screening Scientific Platform workflow

 

Main applications:

1. HTS/HCS

1.1 Compound screening 

The platform has access to compound libraries allowing to screen thousands of small molecules on cells or even all organisms. Typical read-outs are luminescence, fluorescence, absorvance or microscopy.

1.2 Genetic screening

The platform is equipped to deal with siRNA, dsRNA, CRISPR/CAS9 screens in high-throughput.

 

 

 

 

 

2. Bioimage data analysis

2.1 Digital image analysis

"Image analysis is a process of discovering, identifying, and understanding patterns that are relevant to the performance of an image-based task. One of the principle goals of image analysis by computer is endow a machine the capability to approximate, in some sense, a similar capability in human beings" in Gonzales, R.C. and Woods, R.E. (1992). 

 

 

2.2 Data Analysis

Proprietary and open-source data analysis softyware is available (GraphPad, Spotfire, CellProfiler Analyst, shinyHTM)

 

 

3. Equipment

3.1 Assay preparation 

The platform is equipped with liquid handling equipment allowing for medium to high throughput sample preparation

 

 

3.2 Data acquisition

The platform reading instruments include multimode microplate readers and high content screening microscope

Assay preparation

* click on the images to watch video tutorials or examples

Multidrop^TM Combi Reagent Dispenser (Thermo-Scientific)

This bulk reagent dispenser quickly dispenses almost any type of liquids from reagents, to cells in suspension, to whole organisms. Can be operated inside safety cabinets. Examples of common applications are: cells seeding, buffer exchanges, fixation and washes. 

 

      

• From 6- to 1536-well plates
• High speed and high precision
• From 0.5 uL to 2500 uL
• From reagents to cells to whole organisms

 

JANUS with 4 Tip Arm and MDT Arm (PerkinElmer)

This automated liquid handling workstation allows for simple to complex pipetting workflows. Examples of common applications are: compound transfer to assay plates, small volume liquid transfer, cherry picking. 

• Automation of sample preparation
• Two pipetting arms: 4-tip Varispan^TM and MDT
• Liquid transfers from any combination of laboratory containers including 384-well plates
• Compound transfer (100 nL pin-tool)
• Up to 24 microplates on the deck at one time (assay plates, tip boxes, reservoirs,...) 

 

Liquidator 96 (Metler-Toledo)

Manual pipetting system. Allows pipetting all 96 wells at once. No need for programming, works as a normal multichannel pipette. Can be operated inside safety cabinets. Examples of common applications are: buffer or reagents transfer, 96 to 384 or reverse re-formatting, small volume transfer. 

     

• Fast and easy pipetting like a manual pipette
• From 5 uL - 200 uL
• Clean, Sterile, Filter Tips
• 96-384 well plates

 

ALPS 50 V-Manual Heat Sealer (Thermo-Scientific)

Microplate heat sealer. Examples of common applications are: sealling plates for reagents incubation or for freezing. 

 

     

• Secures tight seals around individual wells
• Sample protection of storage and reaction plates in applications including compound storage, sample archiving and PCR
• Wide range of hot seals, including piercable, optically clear and permanent

 

Cell culture resources 

The platform has independent cell culture equipment for projects being developed in the platform. 

 

Data Acquisition

IMAGERS

IN Cell Analyzer 2000 (GE Healthcare)

High content analysis system equipped with a fully automated widefield fluorescence microscope. 

 

 

 

• Widefield microscope (objectives 2x/0.1, 10x/0.45, 20x/0.45, 40x/0.95)
• Imaging from glass slides up to 1536-well plates
• Fixed end-point assays or live-cell studies (temperature and CO2 control)
• Mosaic acquisition

 

Operetta CLS (Revvity)

High content analysis system equipped with a fully automated widefield (8 LED) fluorescence microscope. 

 

 

 

 

 

 

• Widefield microscope (objectives 1.25x Air/0.03, 5x Air/0.16, 10x Air/0.3, 20x Air/0.4, 20x Water/1.0, 40x Water/1.1, 63x Water/1.15)
• Imaging from glass slides up to 1536-well plates
• Fixed end-point assays or live-cell studies (temperature and CO2 control)
• Mosaic acquisition
• PreciScan Intelligent Acquisition

 

Opera Phenix Plus (Revvity)

High content screening system equipped with a fully automated widefield/confocal fluorescence microscope. 

 

 

 

 

 

• Widefield/Confocal microscope (objectives 1.25x Air/0.03, 5x Air/0.16, 10x Air/0.3, 20x Air/0.4, 20x Water/1.0, 40x Water/1.1, 63x Water/1.15)
• High power lasers (405, 488, 561, 640 nm)
• 4x sCMOS cameras
• Imaging from glass slides up to 1536-well plates
• Fixed end-point assays or live-cell studies (temperature and CO2 control)
• Mosaic acquisition
• PreciScan Intelligent Acquisition
• Integrated with cell::explorer

 

 

 

 

 

 

 

 

 

 

MULTI-MODE MICROPLATE READERS

Synergy 2 (BioTek)

High throughput multi-detection microplate reader. Examples of common applications are: absorvance measurements, visible wavelenght fluorescence measurements and glow luminescence levels.

 

     

• Fluorescence Intensity (filter-based: 360/460, 485/528, 540/620)
• Luminescence
• Polarized fluorescence
• Time resolved fluorescence
• UV-visible Absorvance
• Temperature control
• Shaker

 

SpectraMax iD3 (Molecular Devices)

Multi-detection microplate reader.

 

 

 

     

 

• Fluorescence Intensity (monochromator)
• Luminescence
• UV-visible Absorvance
• Temperature control
• Shaker

 

VICTOR Nivo (Revvity)

Multi-detection microplate reader integrated with cell::explorer.

 

 

 

 

 

     

 

• Fluorescence Intensity (filter-based)
• Absorvance
• Luminescence
• Fluorescence intensity
• Time resolved fluorescence
• Fluorescence polarization
• Alpha
• Temperature control
• Shaker

 

Image Analysis

The scientific platform has powerful computer workstations and server to perform digital image analysis. Examples of common applications are: image processing, segmentation and quantification.

Image analysis software

             

 

Image/Data visualization and statistical analysis software

         

 

 

The platform has an open-access policy and the resources are available to the internal and external scientific community and industry. Different usage fees apply.

We can also provide consumables and reagents to perform the screening and high-content microscopy experiments. Please contact us.

 

 

EXTERNAL REQUESTS

The platform has an open-access policy and the resources are available to the internal, external scientific community and industry. 

In order to request an external service or collaboration please fill the form in the following link: 

External Request

In the context of the scientific platform daily work we provide training and assistance to all the users of the equipment. 

 

We also provide for the scientific community (internal and external) international courses and workshops:

Course on High Throughput Screening and Image Analysis for BioSciences

Workshop on BioImage Analysis for High Content Screening 

Please check the Advanced Training schedule to join our next edition.

Bioimage analysis (HCS) workflows

1. Development of an automated image analysis protocol for quantification of intracellular forms of Leishmania spp. Gomes-Alves AG^co, Maia AF^co, Cruz T, Castro H, Tomás AM (2018) PLOS ONE 13(8): e0201747. 
2. Collar occupancy: A new quantitative imaging tool for morphometric analysis of oligodendrocytes. Filipa Bouçanova^co, André Filipe Maia^co, Andrea Cruz, Val Millar, Inês Mendes Pinto, João Bettencourt Relvas, Helena Sofia Domingues (2017) JOURNAL OF NEUROSCIENCE METHODS 294:122-135. 

Other platform publications

1. Maia, A. F. and Gomez-Lazaro, M. (2021). High-content microscopy. In Imaging Modalities for Biological and Preclinical Research: A Compendium (ed. Walter, A.), Mannheim, J.), and Caruana, C.), p. I.1.d-1-14. Institute of Physics Publishing.
2. Pinto, M. F., Figueiredo, F., Silva, A., Pombinho, A. R., Pereira, P. J. B., Macedo-Ribeiro, S., Rocha, F. and Martins, P. M. (2021). Major Improvements in Robustness and Efficiency during the Screening of Novel Enzyme Effectors by the 3-Point Kinetics Assay. SLAS discovery?: advancing life sciences R & D 26, 373–382.
3. Ferreira, J. R., Teixeira, G. Q., Neto, E., Ribeiro-Machado, C., Silva, A. M., Caldeira, J., Leite Pereira, C., Bidarra, S., Maia, A. F., Lamghari, M., et al. (2021). IL-1β-pre-conditioned mesenchymal stem/stromal cells’ secretome modulates the inflammatory response and aggrecan deposition in intervertebral disc. European cells & materials 41, 431–453.
4. Fernandes, A. S., Pombinho, A., Teixeira-Duarte, C. M., Morais-Cabral, J. H. and Harley, C. A. (2021). Fluorometric Liposome Screen for Inhibitors of a Physiologically Important Bacterial Ion Channel. Frontiers in microbiology 12, 603700.
5. Biselli, S., Alencastre, I., Tropmann, K., Erdmann, D., Chen, M., Littmann, T., Maia, A. F., Gomez-Lazaro, M., Tanaka, M., Ozawa, T., et al. (2020). Fluorescent H2 Receptor Squaramide-Type Antagonists: Synthesis, Characterization, and Applications. ACS medicinal chemistry letters 11, 1521–1528.
6. Henriques, P. C., Costa, L. M., Seabra, C. L., Antunes, B., Silva-Carvalho, R., Junqueira-Neto, S., Maia, A. F., Oliveira, P., Magalhães, A., Reis, C. A., et al. (2020). Orally administrated chitosan microspheres bind Helicobacter pylori and decrease gastric infection in mice. Acta biomaterialia.
7. Pádua, D., Barros, R., Amaral, A. L., Mesquita, P., Freire, A. F., Sousa, M., Maia, A. F., Caiado, I., Fernandes, H.,Pombinho, A., et al. (2020). A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin. Cancers 12,.
8. Gomes, R. N., Borges, I., Pereira, A. T., Maia, A. F., Pestana, M., Magalhães, F. D., Pinto, A. M. and Gonçalves, I. C. (2018). Antimicrobial graphene nanoplatelets coatings for silicone catheters. Carbon.
9. Palha, A. M., Pereira, S. S., Costa, M. M., Morais, T., Maia, A. F., Guimarães, M., Nora, M. and Monteiro, M. P. (2018). Differential GIP/GLP-1 intestinal cell distribution in diabetics’ yields distinctive rearrangements depending on Roux-en-Y biliopancreatic limb length. Journal of Cellular Biochemistry 46, 1954.
10. Rocha, H., Maia, A. F. and Gassmann, R. (2018). A genome-scale RNAi screen for genetic interactors of the dynein co-factor nud-2 in Caenorhabditis elegans. Scientific Data 5, 180047-- 8.
11. Cruz, A., Domingues, S., Maia, A. F., Relvas, J. B. and Pinto, I. M. (2017). Identification of actomyosin-based biomarkers relevant for microglia activation. Glia 65, E154-- E155.
12. Silva, A. M., Almeida, M. I., Teixeira, J.H., Maia, A.F., Calin, G. A., Barbosa, M.A. and Santos, S. G. (2017). Dendritic Cell-derived Extracellular Vesicles mediate Mesenchymal Stem/Stromal Cell recruitment. Scientific Reports 1–15.
13. Teixeira, G. Q., Pereira, C. L., Ferreira, J. R., Maia, A. F., Gomez-Lazaro, M., Barbosa, M. A., Neidlinger-Wilke, C. and Gonçalves, R. M. (2017). Immunomodulation of human mesenchymal stem/stromal cells in intervertebral disc degeneration: insights from a proinflammatory/degenerative ex vivo model. Spine.
14. Pinto, A. T., Pinto, M. L., Cardoso, A. P., Monteiro, C., Pinto, M. T., Maia, A. F., Castro, P., Figueira, R., Monteiro, A., Marques, M., et al. (2016). Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities. Scientific Reports 6, 18765.

PT-OPENSCREEN - Portuguese Network for Screening

EU-OPENSCREEN - European Research Infrastructure Consortium (ERIC) for chemical biology and early drug discovery

PPBI – Portuguese Platform of BioImage

CoreEuStem - European Network for Stem Cell Core Facilities

NEUBIAS – Network of European BioImage Analysts

COMULIS - Correlated Multimodal Imaging in Life Sciences

Adher N Rise - ADHEsion GPCR Network

GENiE – Collaborative European Network of C.elegans early-stage researchers and young investigators