Newsletter

Innovate the way we see life | Tomocube Inc. | November 2025

Welcome to the November edition of the Tomocube newsletter.

Advances in label-free microscopy are reshaping how scientists study living systems. This broader movement is captured in the Nature Methods technology feature “Life Beyond Labels,” where global scientists—and Tomocube CEO Yongkeun Park—discuss the growing shift away from perturbative fluorescence methods toward imaging techniques that preserve true biology.

Holotomography stands at the forefront of this transition. By reconstructing quantitative 3D refractive-index maps from LED-based holographic data, researchers can visualize live cells, tissues, and organoids exactly as they are—without dyes, phototoxicity, or sample preparation that distorts physiology.

Nature methods: Life beyond labels
Figure: Holotomography (HT) imaging of scLSECs during expansion, specification, and post-differentiation culture.

As more research groups adopt label-free tools to study sensitive or physiologically relevant systems, holotomography is increasingly being used not just as an alternative, but as a necessary method for questions that conventional approaches fall short.

In this issue, we also highlight two recent studies where holotomography made the difference—unlocking biological insights that required a non-invasive, label-free approach.

Human Stem Cell-Derived Liver Sinusoidal Endothelial Cells

Aspects of zone-like identity and holotomographic tracking of human stem cell-derived liver sinusoidal endothelial cells.

Amirola-Martínez, Mikel et al. Frontiers in Cell and Developmental Biology, https://doi.org/10.3389/fcell.2025.1528991

Researchers addressed the scarcity of primary liver sinusoidal endothelial cells (LSECs) by generating liver sinusoidal endothelial–like cells (scLSECs) from human pluripotent stem cells, recapitulating key features of native liver endothelium.

To study these delicate cells without phototoxicity, they turned to holotomography:

  • Label-free pore visualization: HT captured the emergence and evolution of pore-like membrane structures resembling fenestrae—essential for liver filtration—without fluorescent staining and at high resolution.
  • Long-term live tracking: The non-invasive nature of HT allowed continuous observation of these fragile endothelial cells, which are highly sensitive to light exposure and stress.
  • Machine learning–based quantification: A custom algorithm analyzed 3D HT images to detect and quantify these nanoscopic pores, enabling objective assessment of dynamic structural changes over time.
Figure: Holotomography (HT) imaging of scLSECs during expansion, specification and post-differentiation culture.
Figure: Holotomography (HT) imaging of scLSECs during expansion, specification, and post-differentiation culture.

Primary Neuron Cultures in Alzheimer’s Disease Models

GPR40 agonist ameliorates neurodegeneration by regulating mitochondria dysfunction and NLRP3 inflammasome in Alzheimer’s disease animal models

Tae-Young, Ha et al. Biomedicine & Pharmacotherapy, https://doi.org/10.1016/j.biopha.2025.118678

Primary hippocampal neurons are highly light-sensitive, making label-based imaging unreliable. Using holotomography, researchers evaluated how the GPR40 agonist TUG469 alleviated mitochondrial dysfunction and reduced neuroinflammation in Alzheimer’s disease models.

  • Reduced phototoxic stress: The label-free approach preserved neuronal viability and avoided oxidative artifacts—critical for studying fragile primary neurons.
  • Live neuronal imaging: Visualized mitochondrial morphology and quantified 3D changes in living primary hippocampal neurons without labels or dyes.
  • Quantitative mitochondrial analysis: 3D refractive-index maps revealed how TUG469 restored mitochondrial volume, network integrity, and membrane potential after amyloid-β–induced damage.
Video S4
Video: Live-cell imaging demonstrated that co-treatment ofAβO withTUG469 preserved neuronal morphology and viability.

Our newsletter this month highlights the accelerating shift toward label-free discovery—and how holotomography is emerging as the essential tool enabling this scientific transition.

If you’re ready to see how label-free 3D imaging can transform your workflows, explore our application portfolio or connect with our team for a personalized demo.

Tomocube is dedicated to advancing biological and medical research with our state-of-the-art optical technologies. Inspired by the philosophy, “Innovate the way we see life”, we continuously push the boundaries of 3D imaging, contributing to groundbreaking discoveries that redefine what’s possible in scientific research.