Lattice Lightsheet Microscopy in Life Science Research - Recent Examples of the Research Community
Technology Application

Lattice Lightsheet Microscopy in Life Science Research

Explore recent application examples from the research community

When ZEISS Lattice Lightsheet 7 was presented to the research community in 2020, it marked a milestone in the development of microscopy techniques for the study of life. For the first time, biologists were given the opportunity to observe subcellular biological processes over longer periods of time – with advanced imaging technology implemented in an easy-to-use device under the premise of maximum accessibility.

Research groups around the world have now tested the technology in practice and can show initial results. This page documents the wide range of applications that benefit from lattice light-sheet microscopy and the impressive findings that could only be obtained with ZEISS Lattice Lightsheet 7:

Gene Expression Signatures in Developing Mouse Embryos

Understanding the early processes of developing life

Both images show a fixed mouse embryo at day 3.5 that is approximately 60 µm in diameter. Spinning Disk: Sample is stained for gamma-H2AX and EdU labeled replicating DNA; ZEISS Lattice Lightsheet 7: Sample is stained against gamma-H2AX and DRAQ5.

Image courtesy: T. Olbrich and M. Kruhlak, National Cancer Institute, National Institutes of Health, USA.

In quick succession, the preimplantational mouse embryo undergoes a series of cellular divisions involving two critical cell fate decisions. These decisions influence the complexity and architecture of the further developing embryo. Understanding how embryonic cells biomolecularly restrict their early developmental potential and promote specific cell commitment helps to provide key insights on cancer plasticity and could improve fertilization protocols.


During the transition from the naive epiblast to a pluripotent state, over 100 cells are organized into an approximately 60-80 µm diameter pre-implantation mouse embryo. To examine the changes in gene expression during this transition, both live and fixed samples are imaged at different timepoints using spinning disk confocal microscopy. The volumetric analysis of cellular expression patterns provides evidence for molecular mechanisms regulating the development of pre-implantation mouse embryos.

To determine which cells are expressing specific cellular markers and how these cells are organized relative to each other requires volumetric imaging of the pre-implantation embryos by confocal microscopy. The embryos at this stage are sensitive to changes in growth environment, structural integrity and phototoxicity. To prevent any aberrant changes in the developmental phenotype, the embryos could not be could not be forced against the cover glass and needed to be imaged quickly and with low phototoxicity. The only available option was to use spinning disk confocal microscopy. This imaging method satisfied the need for low phototoxicity, and almost provided the speed required, but suffered from the dramatic loss in signal intensity with increased imaging depth into the embryos. Consequently, only halfway through the depth of the samples were typically imaged.


The ZEISS Lattice Lightsheet 7 microscope enabled imaging of the entire depth of the embryos with little to no phototoxicity, at the required speed to prevent any motion artefacts, and with minimal loss of signal intensity. In addition, the volumetric imaging of the embryos using ZEISS Lattice Lightsheet 7 allowed nearly isotropic resolution for a more accurate representation of the cellular organization within the embryo. Importantly, this imaging technology will allow us measurement of gene expression signatures during this crucial stage in embryonic development.

Acquisition Parameters

Imaged volume: 230 µm x 124 µm x 94 µm, 30 ms exposure time, 30 x 1000 Lattice Lightsheet, two channels.

Living Stem Cell Derived Cardiomyocytes

Investigating cardiovascular diseases with beating heart cells

This video shows live iPS (induced pluripotent stem cells)-derived beating heart cells stained with SiR-Hoechst to label DNA, aquired with ZEISS Lattice Lightsheet 7.

Image courtesy: Y. Taniguchi, Kyoto University, Japan.

The Taniguchi Lab focuses on developing new technologies leveraging the strengths of combining multiple academic fields including biology, chemistry, physics, medicine and informatics. Their multi-disciplinary approach and expertise attracts collaborations with many research groups at the University of Kyoto. In one of their projects, live iPS (induced pluripotent stem cells)-derived cardiomyocytes are investigated as a valuable tool for cardiovascular research. They can be used to model cardiovascular diseases, accelerate drug tests, and advance potential regenerative therapies.



Conventional confocal microscopy cannot image the entire 3D cell model with a temporal resolution higher than the beating frequency.


The capability of ZEISS Lattice Lightsheet 7 to perform fast volumetric imaging with subcellular resolution can be used to investigate tissue variations, such as cellular contractility and viability, among others.

Acquisition Parameters

One volume every 1.26 sec, 48 vol/min for 1 min, imaged volume: 300 µm x 435 µm x 125 µm, 2 µm step size, 126 planes per volume, 1 ms exposure time, 100 x 1800 Lattice Lightsheet.

Axonal Growth Cones on Challenging Grid Structures

Gaining insights into neuronal development and dysfunction

Here, you can see dispersed culture of mouse cortical neurons grown on 200 µm thick cyclo olefin polymer (COP) with a grid structure. Neurons are labelled with mScarlet (cytosol) and Lyn-tailed-EGFP (plasma membrane).

Image courtesy: M. Kengaku, Kyoto University, Kyoto, Japan.

Axonal growth cones explore the environment and determine the direction of neural growth. Investigating the dynamic movement of developing neurons allows a deeper understanding of neural development and dysfunction in neurological and neurodegenerative diseases.


Cells are grown on cyclo olefin polymer (COP) with a grid structure to observe how growth cones progress along the grid. Growth cones are extremely light sensitive and start shrinking when exposed to too much excitation light. Additionally, the grid structure on COP poses many challenges to traditional imaging systems. Double image artifacts can be seen when using a traditional laser scanning confocal. COP also has a refractive index of 1.53, whereas glass has a refractive index of 1.52, and the thickness of the COP bottom is 200 µm; these parameters can cause image blurring.


ZEISS Lattice Lightsheet 7 is able to overcome these challenges. By orienting the grid structure to be parallel to the lattice light-sheet and adjusting the Lattice Lightsheet 7-specific free-form optics, the double image can be removed. Additionally, the gentleness of ZEISS Lattice Lightsheet 7 is the perfect tool to investigate the dynamic movement of developing neurons in 4D with high spatiotemporal resolution without disturbing them with too much light.

Acquisition Parameters

One volume every 15 sec., 21 volumes in 5 min., imaged volume: 78 µm x 44 µm x 22 µm, 0.3 µm step size, 134 planes per volume, 20 ms exposure time, 30 x 1000 Lattice Lightsheet, two channels.

Human Pluripotent Stem Cell Colonies

A promising tool for regenerative medicine

Here, you can see human embryonic stem cell-derived spinal cord organoids in cell culture media and Matrigel labeled EGFP-tagged tight junctions, nuclear mCherry and SiR-actin far red dye.

This timelapse shows micropatterned human pluripotent stem cell (hPSC) colonies expressing tight junction protein 1 fused to green fluorescent protein (TJP1-GFP). These colonies fold into hollow three-dimensional spheres in response to the addition of extracellular matrix. In this instance, the folding process is visualized by a reporter of tight junctions, which localize to the apical side of epithelial hPSCs.

Image courtesy: G. Anand, S. Ramanathan, Harvard University, USA.

The Ramanathan lab seeks to understand decision making by cells and organisms. One research focus is how multi-potent stem cells make developmental decisions to pattern the complex tissues of the human body. Human pluripotent stem cells are a valuable tool to study cell differentiation. As they can re-new indefinitely as well as develop into every other cell type in the body, they hold the potential to replace damaged or diseased cells making them a promising tool for regenerative medicine.


In previous experiments using confocal microscopy, photobleaching and phototoxicity issues were creating problems with data collection.


ZEISS Lattice Lightsheet 7 enabled volume imaging of the spheres to track cell divisions and rearrangements.

Acquisition Parameters

One volume every 10 min for 16 hrs, 97 volumes were recorded, imaged volume: 520 µm x 540 µm x 32 µm, 12ms exposure time, 100 x 1800 Lattice Lightsheet.

We were interested in evaluating ZEISS Lattice Lightsheet 7 to see if it would overcome our problems with photobleaching and phototoxicity, which we experienced when attempting to image our fluorescent reporter cell lines at high temporal resolution using conventional confocal microscopy. We were pleasantly surprised by the ability to capture dynamic movements of cells at timescales of under 5 minutes using this instrument. We thank ZEISS for the opportunity to image our samples using their latest technologies.

Giridhar Anand

Ramanathan Lab, Harvard University, USA

Mitotic Events with Subcellular Detail

Investigating the possible connections between mitochondria and the actin cytoskeleton

This video shows HeLa cells expressing LifeAct-GFP to label actin (green) and Tom20-mCherry to label mitochondria (blue).

Localization of mitochondria in different regions of cells is mediated through the actin cytoskeleton. We are looking at the molecular mechanisms governing this process and aim to observe interactions between mitochondria and the action cytoskeleton in proliferating cells.


Phototoxicity is observed with these samples when using traditional confocal microscopy.


ZEISS Lattice Lightsheet 7 enables imaging of cells for 12 hours with enough resolution to image actin and individual mitochondria, even during mitotic events.

Acquisition Parameters

Five positions, one volume every 10 minutes for 12 hours, 73 volumes were recorded, imaged volume: 75 µm x 120 µm x 16 µm per position, 30 ms exposure time, 30 x 1000 Lattice Lightsheet, three channels.

Brain Organoids

Simulating the brain to study neurological disorders and neurodegenerative diseases

This video shows a brain organoid.  Image courtesy: Maria La Calle Aurioles, McGill University, Montreal, Canada.

Brain organoids are self-organizing three-dimensional tissue structures derived from stem cells and able to simulate the architecture and functionality of the human brain. They are widely used to study the brain, neurological disorders, and neurodegenerative diseases.


Conventional confocal microscopy requires a compromise on either speed or resolution to image the entire brain organoid in a reasonable amount of time.


ZEISS Lattice Lightsheet 7 images the entire organoid with enough resolution to distinguish individual neurons in under 10 minutes.

Acquisition Parameters

Imaged volume: 1.37 mm x 1.18 mm x 76 µm, 5 ms exposure time, 100 x 1800 Lattice Lightsheet, two channels.

Zebrafish Intersegmented Vessel

Investigating cardiovascular development in zebrafish embryos

This is a live day 6 zebrafish expressing dsRed to label blood vessels (purple) and GCaMP/GFP to measure calcium signaling (green).

Image courtesy: J. Mack, University of California, Los Angeles, USA.

The Mack Lab studies the mechanisms of endothelial mechanotransduction in the context of vascular health and disease. They study how blood flow forces influence vascular response- both at the single cell and tissue level. To visualize the heterogeneity of response, they utilize high resolution live cell imaging and atomic force microscopy to quantify the dynamics of Ca2+ oscillations, measure flow induced plasma membrane properties and determine the localization of proteins at the subcellular level.1

Zebrafish is a model organism widely used in cardiovascular research as they reproduce fast, the embryos are transparent, and genetic manipulation is straightforward. The Mack Lab uses zebrafish to study cardiovascular development, function, and diseases.  

Challenges and Solution

Widefield microscopy provided the speed required for live imaging of endothelial cells of blood vessels but only with ZEISS Lattice Lightsheet 7 could higher resolution, particularly in the axial dimension, be achieved.

Acquisition Parameters

One volume every 8 sec for 15 min, 115 volumes were recorded, imaged volume: 200 µm x 250 µm x 55 µm, 3ms exposure time, 100 x 1800 Lattice Lightsheet, two channels.

Membrane Ruffling in Cancer Cells

Characterizing tumor cell motility and metastatic potential

This video shows cancer cells expressing membrane tagged GFP.

Image courtesy: I. Smith, University of California, Irvine, USA.

Membrane ruffling is a dynamic movement of the cell surface membrane often observed at leading edge of adherent cells. In cancer cells, membrane ruffling can be used to characterize tumor cell motility and metastatic potential.

Challenges and Solution

ZEISS Lattice Lightsheet 7 allows for volumetric imaging of ultra-fast membrane dynamics with near-isotropic resolution for detailed characterization of membrane ruffling.

Acquisition Parameters

One volume every 1.5 sec for 2 min, 85 volumes were recorded, imaged volume: 58 µm x 60 µm x 9 µm, 3 ms exposure time, 15 x 550 Lattice Lightsheet.

Neural Labelling in living C. elegans

Investigating neurodegenerative human diseases in C. elegans

Here, you can see  C. elegans with different neural labels.

Image courtesy: S. Encalada, The Scripps Research Institute, and S. Chalasani, Salk Institute, La Jolla, USA.

The Encalada lab is interested in characterizing the interactions between molecular motors and their vesicular cargo to regulate axonal transport in neurons. One tool they use is high-resolution microscopy in C. elegans, to identify and characterize motor-cargo regulatory complexes. They also use C. elegans to build models of protein aggregation diseases including prion diseases and Alzheimer’s disease to characterize the role of motor-based transport in toxicity and infectivity.1

The Chalasani lab uses the simple nervous system of C. elegans to study human disease and drug testing in a well-understood model.2


Imaging neurons in an entire C. elegans requires ultra-fast imaging of large volumes – which is challenging for technologies such as traditional confocal microscopy.


ZEISS Lattice Lightsheet 7 not only provides the required temporal resolution but also the spatial resolution to identify and follow individual neurons in the moving worm.

Acquisition Parameters

One volume every 2 min for 1 hr 20 min, 41 volumes were recorded, imaged volume: 300 µm x 340 µm x 55 µm, 15 ms exposure time, 100 x 1800 Lattice Lightsheet, two channels.

Cytotoxic T Cell Targeting Melanoma Cells

Studying T cell behaviour to optimize immunotherapy

These videos show cytotoxic T lymphocytes interacting with mouse melanoma target cells. Lymphocyte is stained with CellVue Maroon and the target cell is expressing F-tractin EGFP, an F-actin reporter.

Image courtesy: Elisa Sanchez, Morgan Huse, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, USA.

The Huse Lab is interested in how immune cells communicate. Effective immune responses against infectious agents and cancer require that immune cells traffic to the correct locations and then identify and specifically respond to threats by physically interacting with other cells. T cells can completely reorganize their structure in a matter of minutes in response to surface receptor stimulation. The Huse lab studies the signaling mechanisms that control T cell architecture and how specific cellular structures contribute to immune function. A better understanding of these issues could aid in the development of strategies to better modulate immune responses in vivo, such as immunotherapy.1

To optimize the effects of immunotherapy, it is crucial to understand how T cells recognize and kill cancer cells.

Challenges and Solution

ZEISS Lattice Lightsheet 7 captures T cells live and in action. Fast, gentle volumetric imaging of cellular interactions with near-isotropic resolution makes it the perfect tool to study T cell behavior and function.

Acquisition Parameters

Three positions, one volume every 3 min for 2 hrs 15 min, 507 planes per volume, imaged volume: 300 µm x 130 µm x 16 µm per position, 25 ms exposure time, 30x1000 Lattice Lightsheet, two channels.

Pancreatic Cancer Organoids

Calcium signaling in cancer research

Here, you can see a pancreatic cancer organoid stained with Calcium indicator dye GCaMP6s.

Image courtesy: Michiyuki Matsuda and Shinya Yamahira, Kyoto University, Japan.

In cancer research, alterations in calcium signaling have been linked to tumor growth and progression. GCaMP is a genetically encoded calcium indicator that fluoresces green when bound to calcium; therefore, GCaMP is commonly used to measure increases in intracellular Ca2+ and to study calcium signaling.


Calcium signaling events are known to be ultra-fast events and capturing the full volume of an organoid quickly enough to not miss such events can be challenging.


ZEISS Lattice Lightsheet 7 enables time-lapse imaging of the whole organoid with high temporal resolution to capture Calcium flashes of individual cells.

Acquisition Parameters

One volume every 10 sec for 10 min, 376 planes per volume, imaged volume: 145 µm x 350 µm x 75 µm, 5ms exposure time, 100 x 1800 Lattice Lightsheet.

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