Automated Laser Microdissection (LMD) for Spatial Omics Research
Spatial omics research is crucial for understanding the spatial organization of biological molecules, providing key insights into cellular function and disease mechanisms. To ensure applicability to large patient cohorts and low sample inputs, including single-cell applications, an automated and high-throughput sample preparation and isolation protocol is crucial. By integrating artificial intelligence (AI) with automated high-throughput laser microdissection (LMD) and mass spectrometry, these demands are effectively met.
Precision at the Single-Cell Level
Automated LMD is an advanced technology that enables the precise and fully automated dissection of tissue, single cells, and even subcellular compartments. With MMI’s high-throughput solution, the CellRobot , hundreds of single cells can be dissected within 96-well plates in less than one hour—streamlining workflows like never before.
The LMD process utilizes patented CapSure technology, ensuring gentle and contamination-free cutting. This innovative approach allows for visual inspection of dissected cells while maintaining their integrity. Additionally, the system boasts an unmatched collection efficiency of nearly 100%, setting a new standard in automated spatial omics research
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Automated LMD Solution by MMI: CellCut + CellRobot
MMI’s automated LMD solution combines the precision of the CellCut Laser Microdissection system with the efficiency of the CellRobot. This powerful integration enables the fully automated isolation of hundreds of cells in each well of a 96-well plate — delivering high-throughput performance with unmatched accuracy and consistency.
Automated LMD for Spatial Proteomics
Cancer arises from cellular dysfunction, often linked to changes in protein abundance or malfunction. As a result, the proteome serves as a vital indicator of health and disease. Notably, protein composition within the cancer microenvironment can vary significantly. Gaining insight into cellular heterogeneity is essential for distinguishing between healthy and diseased states.
Automated Isolation of single cells in 96-well plates
The combination of MMI’s automated high-throughput Laser Microdissection (LMD) with ultra-high sensitivity mass spectrometry delivers unprecedented molecular insights with spatial context at the cellular level. This innovative approach enables the separation and annotation of individual proteomes from both cancerous and healthy cells within the same microenvironment. Furthermore, the system allows for the precise isolation of single cells into 96-well plates, facilitating downstream analysis with high accuracy and efficiency.
We appreciate the resistant MMI product quality, the professional consulting, and the competent and quick service. MMI instruments are an important basis for our in-situ analysis of cellular tissue. The MMI CellCut laser microdissection for cell isolation followed by gene expression analysis is complementary to further routine methods like conventional optical microscopy (fluorescence), in-situ hybridization, and immunohistochemistry.
CellCut achieves a 100% success rate in single cell and subcellular collection, helping us discover new immunosuppressive cell subtypes in pancreatic cancer, with significant publications forthcoming.
URWTH Aachen, Germany
“I have compared all current available LMD platforms thoroughly and I got to say the CellCut plus is the most impressive one and I highly recommend it to our colleagues. Thanks for bring it to me.”
Chinese Academy of Sciences
Guangzhou, China
AI-Driven Image Analysis Meets LMD
The integration of Artificial Intelligence (AI) with LMD, enhances workflow efficiency and increases throughput. AI automatically detects cells based on defined phenotypic characteristics, marking them for precise isolation. The coordinates of these selected cells (ROI) are then imported into the LMD system, ensuring precise and accurate dissection for downstream analysis.
Use established AI analysis software
Separate AI-based imaging analysis software, such as StrataQuest, BIAS, or the MMI CellDetector, can be used to analyse cell phenotypes. The cell shapes are then imported and aligned into the LMD Software. For alignment, three reference points are required and matched with the live image in the LMD system, ensuring seamless integration of imaging and dissection workflows.
Maximum compatibility with all data formats
All data formats, including XML or JSON, are supported, ensuring maximum compatibility and flexibility in data processing.
The image shows melanoma cells detected by BIAS after alignment with the LMD system.
Unique Collection using 96-Well Plates
The MMI automated LMD system CellRobot uses a specially designed 96-well plate, with each well featuring an elastic silicone membrane. Tissue samples mounted on Membrane Slides are placed beneath this plate. When a target cell is precisely excised by the MMI laser, an automated puncher mechanism gently stretches the silicone membrane to collect the dissected cell directly into the corresponding well.
Contamination-free collection of single cells
During the isolation process, the silicone of the plate only comes into contact with the membrane of the slide, not with the cell itself. This ensures that each single cell is isolated without contamination.
Automated isolation of hundred of single cells
The procedure can be repeated multiple times for each well of the plate, allowing for the collection of hundreds of single cells from one sample, without any overlap between the cells. After automated isolation, the silicone plate is transferred onto a standard 96-well plate, where the collected cells are now located at the bottom of each well—ready for immediate downstream applications.
Our team at the University of Utah had the opportunity to trial the CellCut system, and the results were immediately impressive. The DNA yield exceeded expectations, outperforming our previous protocol. The CellCut system offered unparalleled precision, using direct „no failure“ capture for complete sample recovery, unlike the Zeiss system’s crypt chunk catapulting. Its gentler laser minimized DNA damage and the silicone-based capture simplified sample transfer.
We were able to prepare 16 successful whole genome sequencing libraries faster than a single capture-to-DNA extraction trial with the Zeiss, where results consistently failed. I am confident the CellCut system will be an invaluable resource for the Human Genetics Department and other research groups at the University of Utah, significantly enhancing both efficiency and outcomes.
University of Utah, Salt Lake City, USA
The Most Gentle Isolation of Single-Cells
Gentle and Precise Single-Cell Isolation
The MMI CellRobot enables the most gentle isolation of single cells. The specialised laser delivers an exceptionally precise cutting edge as thin as 0.3 µm. This precision protects the surrounding tissue and preserves biological information.
Advanced Laser Technology for Optimal Results
The system’s low-energy laser (pulse energy ≤ 2 µJ) ensures that even delicate samples remain undamaged during cutting. At the same time, its high pulse rate (4 kHz) provides enough power to effectively dissect even thicker tissue sections. By moving the sample stage rather than the laser beam, the CellRobot maintains constant focus and a consistently minimal cutting edge — ensuring optimal results every time.
Case Study:
Multimodal Single Cell-Resolved Spatial Proteomics Reveal Pancreatic Tumor Heterogeneity
Next-Level Precision in Single-Cell Proteomics
Understanding the proteomic basis of intra-tumor cell diversity—especially in complex cancers such as pancreatic tumors—remains a major challenge in cancer research. Profiling proteins at single-cell resolution within their native spatial context is crucial, yet difficult to achieve with conventional techniques. To address this, Prof. Ruijun Tian and his team have developed a powerful new approach that combines image-guided spatial proteomics with fully automated laser microdissection. This innovative method enables researchers to investigate cell-type heterogeneity directly within tissue samples.
Combining Advanced Imaging and AI with no-failure automated LMD
Ruijun Tian and his team developed a platform that integrates multiple cutting-edge technologies, including high-quality multiplexed imaging and automated laser microdissection (LMD) with single-cell resolution. Regions of interest (ROIs), corresponding to individual cells, were identified using AI-driven deep learning models. These detected cell shapes were transferred to the MMI automated LMD system, where they were aligned in real time with the LMD image using three reference points. For accurate alignment, the three reference points have to be selected from recognisable features of the sample on the whole slide image. After importing the shapes, these points are identified on the live image of the LMD system for precise alignment of the cell shapes. Following this precise alignment, hundreds of single cells were automatically dissected and collected. Crucially, the MMI CellCut / CellRobot system achieved a 100% success rate in the isolation process, with no collection failures. This level of precision and reliability was instrumental in ensuring that hundreds of intact single cells could be isolated and processed for downstream liquid chromatography-mass spectrometry (LC-MS) analysis.
Outcome: A Scalable Workflow for Spatial Proteomics
This study delivers a streamlined and scalable proteomics workflow, offering new insights into cellular heterogeneity within tissues and paving the way for more refined spatial biology research.
"Our experience for cell isolation with MMI CellCut has been overwhelmingly positive. Its flexibility and user-friendly interface allowed seamless integration of diverse imaging and proteomic data, enhancing our analysis of tumor and neural heterogeneity.
CellCut achieves a 100% success rate in single cell and subcellular collection, helping us discover new immunosuppressive cell subtypes in pancreatic cancer, with significant publications forthcoming."
Shenzhen, China
MMI vs. Gravity-Based Systems
An independent benchmark study highlights the significant advantages of MMI’s efficient single-cell collection compared to the traditional gravity-based LMD system. The comparison focuses on collection efficiency, particularly when isolating cells with precise contours at single-cell resolution
No-failure collection
While gravity-based methods frequently result in sample loss, MMI’s approach ensures a 100% successful isolation of single-cells. This reliability is essential for sensitive downstream applications where every single cell matters.
The videos below provide a direct visual comparison between the two technologies. They clearly demonstrate how gravity-based collection often fails to retain isolated samples, whereas MMI consistently captures each selected cell with complete accuracy.
Documents: Automated LMD
Brochure – Spatial Proteomics
From Cell to Insight
Brochure
Just Cut It!
