EPISODE 62: The Worm in a Single Shot

Welcome to the next episode of The Worm Podcast 🔬

This week we are looking at two very different developments in microscopy — one that captures three-dimensional fluorescence in a fraction of a second, and another that adds multiple quantitative imaging modes using a compact, open-source illuminator costing around £100.

Together, they ask:

what happens to biology when microscopes become faster, gentler and more accessible?

⚡ An entire 3D worm in a single exposure

Three-dimensional fluorescence imaging usually means building a z-stack one focal plane at a time.

Light-field microscopy does something very different.

A microlens array captures multiple views simultaneously, encoding the information needed to reconstruct a three-dimensional volume from a single exposure.

In the first paper, whole-worm fluorescence volumes were reconstructed as 121 axial slices spanning 109 µm, with three fluorescence channels acquired in a combined exposure time of just 112 milliseconds. 2026.09.07.749827v1.full (1)

The authors tested FM1-43, FM4-64 and Nile Red delivered either through labelled bacteria or by direct liquid exposure.

And the route mattered.

The same fluorescent probe produced different spatial patterns depending on how it reached the worm. 2026.09.07.749827v1.full (1)

🌌 Meet COSMIC

The second development starts at the illumination side of the microscope.

COSMIC — Compact Open-Source Multimodal Illumination Cluster — is a condenser-free system made from LEDs, 3D-printed components and open-source electronics.

For roughly £100 in materials, it can add:

• bright field
• dark field
• fluorescence
• differential phase contrast
• quantitative phase imaging

to commercial and open-source microscope platforms. 2026 Ewan Microscopy Paper

🧠 Measuring without labels

Quantitative phase imaging extracts information from transparent specimens without fluorescent labels.

Rather than simply creating contrast, phase measurements can provide information related to properties such as morphology, volume and dry mass. 2026 Ewan Microscopy Paper

COSMIC was demonstrated from live cell systems through to whole C. elegans, showing how different imaging modes can reveal complementary information from the same specimen. 2026 Ewan Microscopy Paper

🔬 What comes next?

These papers point towards a future where microscopy becomes increasingly computational, multimodal and accessible.

Imagine combining rapid 3D fluorescence with label-free quantitative measurements, intrinsic autofluorescence and behavioural imaging — capturing more dimensions of biology while exposing living organisms to less light.

That could reveal biology we currently miss simply because our microscopes are too slow, too invasive or too specialised.

🧠 The take-home message

Better microscopy is not just about sharper pictures.

It changes the questions we can ask.

One technology captures a whole fluorescent volume almost instantly.

The other makes sophisticated quantitative imaging available with remarkably simple hardware.

Together, they offer a glimpse of what the next generation of whole-organism microscopy might look like.

📄 Papers discussed

Robert Markus, Edward Rea, Nana A. Berfi, Vincenzo Taresco, Chris Hudson, Dominic R.A. White and Veeren M. Chauhan (2026)

Single-shot light-field microscopy captures delivery-dependent dye and autofluorescence patterns in Caenorhabditis elegans

bioRxiv

DOI: https://doi.org/10.64898/2026.09.07.749827

Ewan Drever-Smith, Flavius C. Pascut, George I. Wadsworth, Veeren M. Chauhan and Kevin F. Webb (2026)

Multimodal illumination for quantitative transmitted-light microscopy

Journal of Microscopy

DOI: https://doi.org/10.1111/jmi.70156

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If you would like your research discussed in a future episode, please contact Dr Veeren Chauhan.

🔗 www.veerenchauhan.com
📧 veeren.chauhan@nottingham.ac.uk