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 on the Acquifer IM high-throughput screening microscope. 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.
case study 1

In-vivo Image-Based Large-Scale Phenotyping

Recent work by Welz et al. 1 demonstrates how live imaging of medaka embryos can be scaled to systematically study phenotype–genotype relationships  in a developing vertebrate. The work combines high-content microscopy to capture embryonic heart rates at large scale with downstream genomic analysis and computational modelling. Together, this work links insights between genotype, dynamic phenotype, and developmental outcome.

This study contributes to a larger body of work by the research groups of Joachim Wittbrodt (COS, Heidelberg) and Ewan Birney (EMBL). Their earlier work established the feasibility of high throughput imaging of heart rates in small vertebrate models under tightly controlled environmental conditions 2. While more recent publications integrated imaging data with automated quantification, machine learning, and scalable bioinformatics pipelines 3. This was complemented by a large-cohort study 4 that demonstrated how these approaches can be applied to identify heart-disease associated genomic features.

Editing of candidate genes affects embryonic heart rate in medaka embryos. Reused Figure 4 from [4] with permission under CC BY 4.0 licence.
Automated imaging of medaka and zebrafish embryos is performed during defined developmental windows of functional cardiovascular activity, with single or multiple embryos mounted per well in microtiter plates without anaesthesia or agarose. Time-lapse image sequences acquired at configurable frame rates and channels are analysed using the HeartBeat software to automatically quantify heart rate, beat-to-beat variability, and cardiac segmentation, with results exported as graphical and spreadsheet outputs. Reused Figure 1 from [2] with permission under CC BY 4.0 licence.

The Bruker Acquifer IM provides the technical foundation required for this class of experiments. Its moving optics architecture enables rapid, repeatable imaging of short time series across multiwell plates while eliminating motion artefacts. The latter is key to robustly and automatically extract embryonic heart rates from acquired datasets. Equally critical, precise and stable temperature regulation ensures robust conditions for studying physiological responses at different environmental parameters. 

Together, these capabilities support the generation of high-quality, time-resolved image datasets that integrate seamlessly with modern image analysis, machine learning, and genomics workflows. As illustrated by the work by Welz et al. 1 and related methodology papers, the Acquifer IM enables scalable, physiologically insightful, image-based assays that bridge microscopy and functional genomics.

References

  1. B. Welz et al., “Discovery and characterization of gene-by-environment and epistatic genetic effects in a vertebrate model,” Cell Genomics, p. 101164, Feb. 2026, doi: 10.1016/j.xgen.2026.101164.
  2. J. Gierten et al., “Automated high-throughput heartbeat quantification in medaka and zebrafish embryos under physiological conditions,” Sci Rep, vol. 10, no. 1, p. 2046, Feb. 2020, doi: 10.1038/s41598-020-58563-w.
  3. M. S. Ferreira et al., “FEHAT: efficient, large scale and automated heartbeat detection in Medaka fish embryos,” Bioinformatics, vol. 40, no. 12, p. btae664, Dec. 2024, doi: 10.1093/bioinformatics/btae664.
  4. J. Gierten et al., “Natural genetic variation quantitatively regulates heart rate and dimension,” Nat Commun, vol. 16, no. 1, p. 4062, Apr. 2025, doi: 10.1038/s41467-025-59425-7.

Specifications

ObjectiveMagnificationNumerical ApertureWorking Distance
CFI P-Achromat UW2X2x0.067.5
CFI Plan Fluor4X4x0.1317.2
CFI Plan Fluor10X10x0.316.0
CFI S P-Fluor ELWD20xC20x0.458.2-6.9
CFI S P-Fluor ELWD40xC40x0.63.6-2.8

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

The Plate-Viewer Software on the Acquifer IM High-Throughput Screening Microscope

Whole Organism Screening: Left: Three day old embryo of the epi:GFP;myl7mR trans­genic line. Zebrafish embryos visualized in the Plate-Viewer software 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.

The Plate-Viewer visualization software utilizes data acquired with the Acquifer IM high-throughput screening microscope. 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 the Plate-Viewer software, showing menus to data as images, stacks, or movies.
Screenshot of the 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
2026 Heidelberg Thesis Modeling human PMM2-CDG in medaka to understand systemic effects of hypoglycosylation on development Pakari Kaisa congenital disorders of glycosylation, PMM2 deficiency, protein hypoglycosylation, embryonic development, medaka precision genome editing, base editing, conditional protein degradation, translational disease modelling, quantitative proteomics
2026 BioRvix preprint Glomerular Endothelial Cell-Derived Extracellular Vesicles Cross the Basement Membrane to Regulate Podocyte Function Janina Kern, Sindhu Thiagarajan, Nina Sopel, Alexandra Ohs, Patricia Luckner, Astrid Bruckmann, Jan Van Deun, Mustafa Kocademir, George Sarau, Silke Christiansen, Christoph Daniel, Mario Schiffer, Stefan Uderhardt, Janina Müller-Deile glomerular endothelial cell, podocyte, vesicle nanoparticle tracking analysis, electron microscopy, RAMAN spectroscopy and flow cytometry.
2025 Heidelberg Thesis Organoid-based studies on the fundamental rules of retinal tissue self-organization and patterning Schlagheck Christina Maria retinal development, organoids, mechanical patterning, cell fate specification, medaka retinal organoid culture, biomechanical manipulation, 3D stem cell models, extracellular matrix supplementation, developmental pattern analysis
2025 Heidelberg Thesis Understanding and modulating molecular mechanisms of peritoneal transport function to improve peritoneal dialysis efficacy and outcome Iva Marinovic peritoneal dialysis, peritoneal mesothelium, solute transport, tight junctions, chronic kidney disease RNA sequencing, in vitro barrier models, immunocytochemistry, single-molecule localisation microscopy, functional transport assays
2025 BioRvix preprint Discovery and characterisation of gene by environment and epistatic genetic effects in a vertebrate model Bettina Welz, Saul Pierotti, Tomas Fitzgerald, Thomas Thumberger, Risa Suzuki, Philip Watson, Jana Fuss, Tiago Cordeiro da Trindade, Fanny Defranoux, Marcio Ferreira, Kiyoshi Naruse, Felix Loosli, Jakob Gierten, Joachim Wittbrodt, Ewan Birney phenotypic plasticity, heart rate regulation, complex traits, gene–environment interaction, medaka QTL mapping, F2 segregation analysis, interaction modelling, gene editing, GWAS power simulation
2025 Heidelberg Thesis Design and implementation of workflow tools for multiplexed time-lapse imaging experiments in zebrafish screening Satheesan Sankeert zebrafish-based screening, multiplexed time-lapse imaging zebrafish, sample preparation, workflow, image analysis
2025 Zeitschrift für Geburtshilfe und Neonatologie Automatisierte Laserablation in der Zebrafischlarve als High-Content Modell für die akute Nierenschädigung und epigenetisches Drug-Screening auf regenerationsmodulierende Substanzen L. Rapp, et al. Acute kidney injury (AKI), regeneration Laser ablation in zebrafish larvae, epigenetic drug screening
2024 MicroPublication Biology Virtual Orientation Tools (VOTj): Fiji plugins for object centering and alignment S. Satheesan, J. Gehrig, LSV. Thomas Sample alignment and orientation Fiji plugin for centering and aligning biological objects
2023 Biospektrum In vivo-Medikamenten-Screening zur Behandlung von Glomerulopathien M. Schindler, S.M. Bach, J. Gehrig, et al. Glomerulopathies In vivo drug screening in zebrafish models
2023 Journal of the American Society of Nephrology A Novel High‑Content Screening Assay Identified Belinostat as Protective in a Focal Segmental Glomerulosclerosis–like Zebrafish Model S. Maximilian Schindler, Florian Siegerist, Tim Lange, Sandra Simm, Sofia M. Bach, Matthias Klawitter, … Nicole Endlich Embryonic/fetal kidney (FSGS-like) High-content screening in zebrafish embryos
2023 Sci Rep Identification of side effects of COVID‑19 drug candidates on embryogenesis using an integrated zebrafish screening platform A. Ernst, I. Piragyte, A. M. MP, N. D. Le, D. Grandgirard, S. Leib, … N. Mercader Embryogenesis, teratogenicity Integrated in vivo zebrafish screening
2023 Nat. Methods EmbryoNet: using deep learning to link embryonic phenotypes to signaling pathways D. Čapek, M. Safroshkin, H. Morales‑Navarrete, N. Toulany, G. Arutyunov, A. Kurzbach, … P. Müller Embryonic development: phenotype–pathway mapping Deep‑learning phenotyping (EmbryoNet)
2023 Front. Cell Dev. Biol. pyHeart4Fish: Chamber‑specific heart phenotype quantification of zebrafish in high‑content screens V. L. Vedder, T. Reinberger, S. M. Haider, L. Eichelmann, N. Odenthal, S. Abdelilah‑Seyfried, … J. Erdmann Cardiac chamber morphology/function High-content imaging + python-based phenotyping
2022 Front. Cell Dev. Biol. The shGlomAssay combines high‑throughput drug screening with downstream analyses and reveals the protective role of Vitamin D3 and Calcipotriol on podocytes M. C. Ristov, T. Lange, N. Artelt, N. Nath, A. W. Kuss, J. Gehrig, … N. Endlich Glomerular podocytes, nephrotoxicity High-throughput drug screening in zebrafish kidney model
2022 eLife Boosting targeted genome editing using the hei‑tag T. Thumberger, T. Tavhelidse‑Suck, J. A. Gutierrez‑Triana, A. Cornean, R. Medert, B. Welz, … J. Wittbrodt Genome editing (CRISPR enhancement) in vivo zebrafish genome editing using hei‑tag
2021 JASN Glomerular Endothelial Cell‑Derived microRNA‑192 Regulates Nephronectin Expression in Idiopathic Membranous Glomerulonephritis J. Müller‑Deile, N. Sopel, A. Ohs, V. Rose, M. Gröner, C. Wrede, … M. Schiffer Glomerular endothelial signaling Molecular biology, in vivo glomerular analysis
2020 Cells A Multiparametric Assay Platform for Simultaneous In Vivo Assessment of Pronephric Morphology, Renal Function and Heart Rate in Larval Zebrafish P. J. Steenbergen, J. Heigwer, G. Pandey, B. Tönshoff, J. Gehrig, J. H. Westhoff Kidney morphology/function + cardiac physiology Multiparametric live zebrafish screening
2019 Int. J. Mol. Sci. A smart imaging workflow for organ‑specific screening in a cystic kidney zebrafish disease model G. Pandey, J. H. Westhoff, F. Schaefer, J. Gehrig Cystic kidney disease Automated organ‑specific imaging
2014 BMC Biotech Generation of orientation tools for automated zebrafish screening assays using desktop 3D printing J. N. Wittbrodt, U. Liebel, J. Gehrig Zebrafish embryo orientation

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