descSPIM-Advanced is an open, modular light-sheet fluorescence microscopy (LSFM) ecosystem designed for cleared-tissue imaging. It builds on descSPIM-basic(desktop-equipped SPIM for cleared specimens), our previously developed open-hardware LSFM platform for tissue-clearing applications. descSPIM-basic was designed to make cleared-tissue LSFM easier to build, operate, and adopt in individual laboratories. descSPIM-Advanced expands descSPIM from a single accessible LSFM design into a scalable and extensible imaging ecosystem
As of April 2026, more than 50 descSPIM-basic systems have been independently built worldwide, demonstrating the accessibility and broad deployability of the original platform.
While descSPIM-basic provided an accessible entry point to cleared-tissue LSFM, advanced applications often require greater imaging flexibility, including larger fields of view, higher spatial resolution, improved illumination, expanded color capability, and simplified deployment.
| Limitation of descSPIM-basic | Need addressed by descSPIM-Advanced |
|---|---|
| Single-side illumination | Dual-side illumination |
| Residual striping in large-volume imaging | Reduced attenuation and striping |
| Low-magnification detection | Higher spatial resolution |
| Three- to four-channel imaging | Super-multicolor / hyperspectral imaging (7–11 colors) |
| Remaining optical and cost complexity | Simpler and lower-cost configurations |
Depending on the selected configuration, descSPIM-Advanced can support:
- large field-of-view whole-organ imaging,
- high-resolution volumetric imaging,
- super-multicolor 3D imaging,
- and low-cost routine cleared-tissue imaging.
In this initial implementation, we demonstrate these capabilities through four interoperable variants — FullMoon, DeepSky, Galaxy, and SLIM — each extending the descSPIM platform toward a distinct imaging regime. These variants are intended as representative implementations within a broader, extensible descSPIM-Advanced design space rather than as a fixed set of system configurations.
A central feature of descSPIM-Advanced is the Mission Control Center (MCC), a shared operational software for the descSPIM family.
MCC provides a Python-based control interface that standardizes operation across both descSPIM-basic and current descSPIM-Advanced implementations. It brings together key microscope functions — including stage movement, camera acquisition, laser control, filter switching, and galvanometric scanner operation — within a unified GUI.
By consolidating hardware control into a single interface, MCC reduces the need for separate software environments and supports reproducible operation across different descSPIM configurations. The only exception is the hyperspectral detector in descSPIM-Galaxy, for which the detector is operated separately using the dedicated Galaxy GUI.
As an initial demonstration of this extensible ecosystem, we propose four interoperable descSPIM-Advanced variants, each optimized for a distinct imaging regime.
| Variant | Main capability | Representative application |
|---|---|---|
| descSPIM-FullMoon | Large field-of-view imaging | Single-field volumetric imaging enabled by a 43-mm sensor-diagonal field of view |
| descSPIM-DeepSky | High spatial resolution | High-resolution volumetric imaging for three-dimensional histology |
| descSPIM-Galaxy | Super-multicolor / hyperspectral imaging | 7–11-color three-dimensional imaging of cleared tissues and optical phantoms |
| descSPIM-SLIM | Low-cost simplified deployment | Rapid, low-cost deployment for 3–4-color cleared-tissue imaging |
descSPIM-FullMoon combines dual-side illumination, light-sheet pivoting, and a 60-MP camera with a 43-mm sensor diagonal to enable large-FOV, single-field volumetric imaging.
descSPIM-DeepSky combines light-sheet pivoting, high-resolution imaging optics, a four-slot filter changer, and a variable slit to support high-resolution 3D histology with improved lateral and axial resolution.
descSPIM-Galaxy integrates dual-camera detection, hyperspectral imaging, a six-slot filter changer, and a dedicated spectral unmixing pipeline to enable super-multicolor cleared-tissue imaging of up to 11 colors.
descSPIM-SLIM adopts an open-top configuration, simplified optics, a variable slit, and affordable laser sources to provide a rapidly deployable and highly accessible configuration at approximately USD 15,000.
Together, these current implementations illustrate how the descSPIM-Advanced ecosystem can span multiple cleared-tissue LSFM regimes, from entry-level, low-cost systems to high-performance configurations for large-volume, high-resolution, and high-channel imaging.
Each implementation includes step-by-step documentation for system construction, optical alignment, image acquisition, and post-acquisition processing.
| Guide type | Contents |
|---|---|
| Optical construction and alignment | Model-specific build manuals and alignment procedures |
| Imaging parameter optimization | Recommended exposure times, laser powers, and detection filters |
| Post-acquisition processing | Registration, stitching, and multicolor alignment workflows |
| MCC installation | Installation guide for the Mission Control Center control GUI |
Note
Build time varies depending on the variant and user experience:
SLIM: 2–5 h from scratch
FullMoon: 9–18 h from scratch
DeepSky: 9–15 h from scratch
Galaxy: 8–14 h from scratch
The Mission Control Center (MCC) is a unified, Python-based control framework for the descSPIM family.
It provides centralized operation of the main hardware modules used across descSPIM-basic and current descSPIM-Advanced implementations, including:
- motorized stages,
- scientific cameras,
- laser sources,
- filter wheels,
- galvanometric scanners,
- and other implementation-specific hardware modules.
The table below summarizes how MCC supports the main hardware configurations across the descSPIM family and the current descSPIM-Advanced implementations.
| System / Variant | Main hardware configuration | MCC support |
|---|---|---|
| descSPIM-basic | Stages, camera, laser source | Fully integrated control |
| descSPIM-FullMoon | Stages, camera, laser source, filter wheel, galvanometric scanner | Fully integrated control |
| descSPIM-DeepSky | Stages, camera, pattern generator, laser source | Fully integrated control |
| descSPIM-Galaxy | Stages, Thorlabs CMOS camera, laser source, filter wheel | Integrated control by MCC |
| descSPIM-SLIM | Stages, camera | Fully integrated control |
Note
In descSPIM-Galaxy, MCC controls the standard microscope hardware components, including the stages, Thorlabs CMOS camera, laser source, and filter wheel.
The hyperspectral detector is controlled separately using the dedicated Galaxy GUI.
For detailed installation, architecture, and developer information, please refer to the dedicated Mission Control Center README.
This work is licensed under a
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
By using descSPIM-Advanced, you agree to the following:
- Academic use only; commercial use requires author permission.
- Modifications and redistribution are allowed under CC BY-NC-SA 4.0.
- Cite the original work in all publications and presentations.
- The authors are not responsible for damages or misuse.
- All disputes shall be governed by Japanese law.
The MCC software is licensed separately. See the MCC directory for its applicable license terms.
- Otomo, K. et al. descSPIM: an affordable and easy-to-build light-sheet microscope optimized for tissue clearing techniques. Nat. Commun. 15, 4941 (2024).
- Susaki, E. A. et al. Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues. Nat. Commun. 11, 1982 (2020).
- Matsumoto, K. et al. Advanced CUBIC tissue clearing for whole-organ cell profiling. Nat. Protoc. 14, 3506–3537 (2019).
- CUBIC-HistoVIsion2.0 protocol
- CUBIC resource website