High-Throughput Screening Microscope

Acquifer IM

Automated microscopy for next-generation widefield imaging and high-content screening

Acquifer IM

Acquifer IM (Imaging Machine) is a fully automated widefield microscope with data storage and processing capabilities ideal for high-content screening assays and phenotypic screening for small-model organisms. Its static sample holder with a mobile optical unit ensures sample stability during imaging, making it ideal for imaging motion-sensitive samples, such as non-adherent cell cultures or embryos.

Intuitive    
design
Provides easy, precise, and robust high-content screening and automated microscopy.
Optimal            
sample-centered approach    
Delivers ideal imaging conditions for sensitive specimens and long-term observations.
Effortless
software workflow
Visualizes large screening datasets and automating centering imaging.
Features

High-Content Screening

The Acquifer IM is a high-performance solution for screening and high-throughput imaging assays and is compatible with all commonly available multi-well plates (adaptions possible). A host of unique features include built-in temperature regulation, a robotic lid, and an open interface for seamless integration into automated workflows. Its comprehensive data storage and processing integrations are ideal for researchers performing high-content or phenotypic screening.

The software and workflow enable low-magnification pre-screen data of a full microtiter plate to be readily visualized in the Plate-Viewer software. Different tools and matching algorithms enable the selection of regions of interest (ROIs) for each well and robust autolocalization of target structures for feedback microscopy.

Acquifer IM is optimized for your high-throughput experiments with:

  • Optimal imaging conditions for sensitive specimens and long-term observations
  • Uniblock optical design moves to your sample while your sample remains stationary
  • Built-in temperature control (20 to 40°C) ± 0.5°C homogeneity over whole plate and over time
Automated timelapse microscopy: HeLa cells with H2B-mCherry imaged every 30 minutes for 48 hours. Courtesy of ALMF, EMBL.
Screening workflows for various assay requirements: Cell culture (left) and a zebrafish xenograft assay (right). Courtesy of Arwin Groenewould.
Applications

Zebrafish Imaging

The Acquifer IM is ideally suited for high-throughput screening of zebrafish, an important preclinical model to study development, disease, and molecular and drug screening. The combination of a static sample holder, a mobile optical unit, and built-in temperature regulation ensures specimen stability during imaging.

Embryonic zebrafish xenograft assay of cancer metastasis. Image courtesy of Arwin Groenewoud (Ewa Snaar-Jagalska lab, Leiden University. RGB changed to magenta-green).
High-content screening for chemical modulators of heart development in zebrafish. Images by 4DHeart ESR Eleonora Lupi (Nadia Mercader lab, University of Bern & Acquifer. RGB changed to magenta-green.).
Whole organism screening with organ-specificity in cystic kidney zebrafish disease models. See also: Pandey et al. 2019 (doi: 10.3390/ijms20061290). Image reproduced under CC BY 4.0 DEED.
High content screening in zebrafish for developmental nephrotoxicity of approved drugs. See also: Westhoff et al., 2020. Image reproduced under CC BY.

Organoid Imaging

Acquifer IM provides invaluable insights into cellular structures and dynamic processes, such as tissue morphogenesis, differentiation, and biophysics. With the ability to conduct high-throughput screenings, it supports the study of developing organoids in combination with advanced genome editing techniques and tissue sections.

Fish-derived organoids differentiating into retinal tissue (green). Courtesy of Venera Weinhardt. Zilova et al., 2021. Image reproduced under CC BY 4.0 DEED.

Other Applications

Tissue section of mouse kidney. Courtesy of Maria Bartosova, Uniklinikum Heidelberg, Germany.
Red dogwood (Cornus sanguinea) – 10x objective, 5x5 positions stitched. Courtesy of Mr Göppert, Karlsruhe, Germany.

Specifications

Objective Magnification Numerical Aperture Working Distance
CFI P-Achromat UW2X 2x 0.06 7.5
CFI Plan Fluor4X 4x 0.13 17.2
CFI Plan Fluor10X 10x 0.3 16.0
CFI S P-Fluor ELWD20xC 20x 0.45 8.2-6.9
CFI S P-Fluor ELWD40xC 40x 0.6 3.6-2.8

IM Dimensions: 553mm (21.77") H x 528mm (20.79") W x 555mm (21.85") D

Add-On Module

Photomanipulation

The photomanipulation module was developed in collaboration with Rapp Optoelectronic, Wedel, Germany, who has over 20 years of experience in high-performance photomanipulation and advanced light microscopy techniques.

Its robust design enables researchers to perform advanced experiments with ease. Full datasets of entire microplates can be annotated and subsequently automatically photomanipulated without further user interaction. This enables large scale photomanipulation for various biomedical assays.

The module is an optional hardware upgrade allowing researchers to easily scale-up complex photomanipulation experiments such as photodamaging of cells and tissues, switch convertible fluorophores, uncage compounds or perform optogenetic activation.

Data by Dr. Jana Heigwer (Westhoff Lab, University Children's Hospital, Heidelberg).
Automated Photomanipulation: GFP-positive distal pronephros of a cdh17:egfp transgenic zebrafish with annotated region of interest (left) and after photodamaging (right).

Acquifer IM Control Software

Software

Plate-Viewer

Whole Organism Screening: Left: Three day old embryo of the epi:GFP;myl7mR trans­genic line. Zebrafish embryos visualized in the Plate-Viewer after automated ROI selection. Courtesy of Nadia Mercader, Uni Bern. Middle: The red bounding box indicates the field of view of a 10X objective used for subsequent high-resolution imaging. Right: Single z-plane of a high-resolution dataset automatically acquired on the Acquifer IM.

Plate-Viewer is the visualization software for data acquired with the Acquifer IM. The user interface and design allow for intuitive working with datasets, such as overviews of screening data, inspection of individual images and functionalities to adjust channels-display, save data visualizations or time-lapse movies.

Both the system and Plate-Viewer have an open interface that enables automated workflows and feedback-microscopy functionalities.

  • Conversion and export of images: Export of single z-planes, z-projections, z-stacks or time-series allows for versatility in data analysis. Also, batch export and various file formats (tif, jpeg, png, bmp, mp4) are available.
  • Feedback Microscopy: Features, such as automated object-detection algorithm and pre-scan ROI-selection enable feedback microscopy.
  • Plugin Interface: Data processing with external software utilizes a plugin interface. Advanced users can generate their own plugins.
Screenshot of Plate-Viewer software, showing menus to data as images, stacks, or movies.
Screenshot of Plate-Viewer software with segmentation based on Stardist/Otsu of nuclei from HeLa cells. Segmentation was performed by calling an external Fiji script via the plugin interface of PV.

Publications

Year Journal Title Author(s) Subject Methodology
2023 Journal of the American Society of Nephrology A Novel High-Content Screening Assay Identified … as Protective in a FSGS—Like Zebrafish Model S Maximilian, S Florian, L Tim, (..) Endlich, Nicole Embryo implantation, morphogenesis Fish, kidney, Acquifer IM
2023 Scientific Reports Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform A Ernst, I Piragyte, A Marwa, (..) Nadia Mercader Embryogenesis, cardiovasculature, COVID-19 Zebrafish embryo model, phenotypic screening
2023 bioRxiv Pre-print Natural genetic variation quantitatively regulates heart-rate and -dimension J Gierten, B Welz, T Fitzgerald, (..) Joachim Wittbrodt Embryonic heart development, Japanese rice fish, genetic mapping, inbred vertebrate model
2023 Nature Methods EmbryoNet: using deep learning to link embryonic phenotypes to signaling pathways D Čapek, M Safroshkin, H Morales-Navarrete, (..) Patrick Müller Signaling pathways, phenotypic defects Zebrafish, machine learning, automated phenotyping, high-throughput drug screens
2023 Frontiers in Cell and Developmental Biology pyHeart4Fish: Chamber-specific heart phenotype quantification of zebrafish in high-content screens V Vedder, T Reinberger, S Haider, (..) Jeanette Erdmann Cardiac chamber-specific parameters Automated quantification, drug screen
2022 ScienceDirect Muscular hydraulics drive larva-polyp morphogenesis A Stokkermans, A Chakrabarti, K Subramanian, (..) Aissam Ikmi Morphogenesis, body contractility and motility, muscle hydraulics and organization cnidarian, quantitative live imaging
2022 Frontiers in Cell and Developmental Biology The ShGlomAssay Combines High-Throughput Drug Screening With Downstream Analyses and Reveals the Protective Role of Vitamin D3 and Calcipotriol on Podocytes MC Ristov, T Lange, N Nath, (..) Nicole Endlich Chronic kidney disease, podocyte de-differentiation Mouse, high-throughput screening, western blot, RNA sequencing
2022 eLife Boosting targeted genome editing using the hei-tag T Thumberger, T Tavhelidse-SuckJose, A Gutierrez-Triana, (..) Joachim Wittbrodt Genome editing, mRNA CRISPR, peptide tags,
2021 Journal of the American Society of Nephrology Glomerular Endothelial Cell-Derived microRNA-192 Regulates Nephronectin Expression in Idiopathic Membranous Glomerulonephritis J Müller-Deile, N Sopel, A Ohs, (..) Mario Schiffer Idiopathic membranous glomerulonephritis (iMGN), MicroRNA-192-5p Zebrafish, mice, cell culture, kidney biopsies
2021 International journal of molecular sciences An Experimental Workflow for Studying Barrier Integrity, Permeability, and Tight Junction Composition and Localization in a Single Endothelial Cell Monolayer: Proof of Concept M Bartosova, D Ridinger, I Marinovic, (..) Sotirios G. Zarogiannis Endothelial and epithelial barrier, cell monolayer Single-molecule localization microscopy, Cell culture, automated imaging and image analysis
2021 eLife Fish primary embryonic pluripotent cells assemble into retinal tissue mirroring in vivo early eye development L Zilova, V Weinhardt, T Tavhelidse, (..) Joachim Wittbrodt Morphogenesis, body contractility and motility, muscle hydraulics and organization Zebrafish, genome editing, quantitative analysis
2021 PLoS ONE In vivo identification and validation of novel potential predictors for human cardiovascular diseases O Hammouda, M Wu, V Kaul, (..) Joachim Wittbrodt Cardiovascular diseases, genome wide association studies CRISPR/Cas9 genome editing, automated high-throughput heart rate analysis
2020 Cells A Multiparametric Assay Platform for Simultaneous In Vivo Assessment of Pronephric Morphology, Renal Function and Heart Rate in Larval Zebrafish P Steenbergen, J Heigwer, G Pandey, (..) Jens Westhoff Chemical toxicity testing, pronephric phenotypes Multiparametric in vivo screening pipeline, 3D-printed orientation tool
2020 Frontiers in Cell and Developmental Biology In vivo High-Content Screening in Zebrafish for Developmental Nephrotoxicity of Approved Drugs J Westhoff, P Steenbergen, L Thomas, (..) Jochen Gehrig Nephrotoxic drugs, phenotypic renal alterations Vertebrate embryos, automated high-content screen, in vivo, microtiter plates
2020 ScienceDirect The human α-defensin-derived peptide HD5(1–9) inhibits cellular attachment and entry of human cytomegalovirus R Böffert, R Businger, H Preiß, (..) Michael Schindler Human cytomegalovirus (HCMV), embryonic development High-content screening, human cells
2020 Scientific Reports Automated high-throughput heartbeat quantification in medaka and zebrafish embryos under physiological conditions J Gierten, C Pylatiuk, Omar Hammouda, (..) Felix Loosli Cardiovascular diseases, genome wide association studies Fish model, screening assay, high-throughput heartbeat analysis
2019 PLoS ONE Enhanced in vivo-imaging in medaka by optimized anaesthesia, fluorescent protein selection and removal of pigmentation C Lischik, L Adelmann, Joachim Wittbrodt Fluorophore selection, specimen immobilization, elminating pigmentation in vivo, fish, light-sheet microscopy, gene editing
2019 PLoS ONE Swift Large-scale Examination of Directed Genome Editing O Hammouda, F Böttger, J Wittbrodt, Thomas Thumberger Isolation and detection of alleles, phenotype-genotype correlation Zebrafish, CRISPR, genetic screening, DIY-pipet tips
2019 International journal of molecular sciences A Smart Imaging Workflow for Organ-Specific Screening in a Cystic Kidney Zebrafish Disease Model G Pandey, J Westhoff, F Schaefer, Jochen Gehrig Glomerular cyst formation, kidney disease Zebrafish, high-content screening, automated imaging, image analysis
2017 Journal of Cell Biology Two distinct membrane potential–dependent steps drive mitochondrial matrix protein translocation A Schendzielorz, C Schulz, O Lytovchenko, (..) Peter Rehling Organelles, trafficking, translocation High-content screening
2016 Proceedings of the National Academy of Sciences δ-COP contains a helix C-terminal to its longin domain key to COPI dynamics and function E Arakel, K Richter, A Clancy, Blanche Schwappach Coat protein I (COPI)-coated vesicles, membrane-associated coatomer High-content screening
2016 Scientific Reports Mice lacking WRB reveal differential biogenesis requirements of tail-anchored proteins in vivo J Rivera-Monroy, L Musiol, K Unthan-Fechner, (..) Fabio Vilardi Tail-anchored (TA) proteins Mouse, in-vivo, high-content screening

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