Tomocube

Research on organoids, the 3D cell aggregates replicating organ structures and functions, benefits significantly from the detailed and noninvasive imaging capabilities of Holotomography (HT). HT efficiently captures the dynamic behavior of cells within living organoids, including mitotic events, cyst formation, and crypt budding. Real-time, high-resolution observations with available quantitative measurements facilitated by HT are crucial for exploring the complex dynamics and morphology of the organoids.

In combination with the HT-ready 96-well plate, which supports a broad spectrum of cell types from 2D to 3D cultures, the HT-X1 is an ideal tool for leveraging the potential of organoids in drug development. It enables high-throughput screenings for rapid assessment of drug response and its toxicity on patient-derived tissues.

A recent study highlighted a successful example of such efforts, demonstrating how HT has set a new standard for comprehensive and rigorous statistical assessments for the biological studies of organoids (Lee et al., 2023). With HT, intricate subcellular structures of individual cells in small intestinal organoids were observed in intricate detail. Long-term monitoring of various biological processes within the specimen, including cell mitosis, migration, apoptosis, and other subcellular dynamics, was achieved effortlessly without the need for labeling or other time-consuming preparations.

Additionally, the observation of morphological changes was combined with quantitative parameters, including organoid volume, protein concentration, and mass, to effectively and comprehensively evaluate the response of the organoids to chemotherapy drug treatments. The study suggested that the Tomocube HT-X1 imaging system is an indispensable tool for organoid-based pharmacological screening applications.

Bridging the Gap Between in vitro and in vivo

Microphysiology systems (MPS) and organ-on-a-chip devices represent the next evolution in physiologically relevant cell culture models. These microfluidic platforms recreate tissue-tissue interfaces, mechanical forces, and fluid flow conditions that are impossible to achieve in static cultures.

Why do traditional imaging methods fall short for MPS? 
Organ-on-a-chip devices present unique imaging requirements:

• Continuous flow systems cannot tolerate fixation or staining protocols
• Scaffold materials often exhibit autofluorescence
• Multi-layer architectures require true 3D imaging capability
• Real-time monitoring is essential for dynamic studies

What advantages does holotomography offer?
Holotomography is uniquely suited for MPS imaging because it requires no sample preparation that would disrupt the carefully controlled microenvironment:

• Non-invasive observation: Image cells on collagen scaffolds and hydrogel matrices without interference
• Real-time monitoring: Track cellular responses to flow conditions and chemical gradients
• Quantitative analysis: Measure cell morphology, proliferation, and viability continuously
• Multi-day experiments: Monitor device function over extended culture periods

Common applications include:

• Liver-on-a-chip for hepatotoxicity screening
• Gut-on-a-chip for barrier function studies
• Lung-on-a-chip for inhalation toxicology
• Vascular chips for endothelial research

The combination of label-free imaging and quantitative 3D analysis makes holotomography an ideal tool for validating and characterizing microphysiology systems during development and application.