iiinova — where your digital self keeps evolving

James Manton @jamesdmanton.bsky.social · 07/10/2026

I am a truly abysmal mathematician, but I have been very fortunate to know many excellent, kind, patient and thoughtful mathematicians over the years. I would be extremely interested to know what they and others make of these recently released results: github.com/openai/math

github.com

GitHub - openai/math

Contribute to openai/math development by creating an account on GitHub.

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Rob Campbell @raacampbell.com · 04/10/2026

Preprint is out! Our BakingTray software turns a 2-photon microscope into a serial-section tomography system for automated whole-organ imaging. ~€35k to convert an existing scope. 11 systems worldwide, >7,000 samples at SWC alone #neuroskyence #microscopy www.biorxiv.org/content/10.6...

A BrainSaw at the Max Planck Institute for Brain Research, Frankfurt. A Nikon 16x water-immersion objective on a 400 µm travel PIFOC allows for fast z-stacks. Samples are imaged and cut in the clear water bath. A Leica VT1000 vibratome is seen to the right with a mounted blade.

How BrainSaw works. Samples are embedded in an agarose block, which is glued to a slide and clamped into a water bath. The bath sits on a three-axis stage under a 2-photon microscope; the stage moves the sample for both tile scanning and slicing. The microscope images the exposed face of the block, the vibratome cuts off the imaged layer, and the cycle repeats until the samples have been fully imaged. Data are stitched automatically and are ready for downstream analysis. Logos below: BrainSaw (hardware), BakingTray (acquisition software), StitchIt (stitching).

Coronal section of an Sst-tdTomato mouse brain imaged on BrainSaw. tdTomato-expressing cells are shown in yellow, scattered through cortex and hippocampus; tissue autofluorescence is shown in blue.

Coronal section of a mouse brain with three neighbouring viral injections targeting layer 5 of V1, expressing mCherry (red), eGFP (green) and BFP (blue). The thick apical dendrites of the labelled neurons are clearly visible, as are their axons projecting to distant targets. Image credit: Alex Fritzl.

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James Manton @jamesdmanton.bsky.social · 02/10/2026

I think there's probably a way, but I also think I don't want to do that...

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James Manton @jamesdmanton.bsky.social · 01/10/2026

Do you have any opinions on how we should do this? Or indeed that we should not do this!?

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James Manton @jamesdmanton.bsky.social · 01/10/2026

Thanks! These are great questions along lines that I've been thinking about, but not doing anything about yet. My original idea was to leave the chunking to HDF5/Zarr, especially as they already do multi-res. There's potentially some inefficiencies there with chunk sizes, but at least it's simple.

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James Manton @jamesdmanton.bsky.social · 30/09/2026

Thanks! Unfortunately, a lot. I’m still working on benchmarking this fairly, but we, for example, do pretty poorly on LICONN data. If you have some data you’d like benchmarking/optimising for please let me know!

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James Manton @jamesdmanton.bsky.social · 30/09/2026

Ooh! That won't solve our 'infinite-time' insane microscope bandwidth problems, but the microscope has to crash at some point, right...? And for all our other microscopes this looks like good fun! Thanks!

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James Manton @jamesdmanton.bsky.social · 29/09/2026

Please bear in mind I've only been working on this since last Wednesday, so things might not be particularly polished...

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James Manton @jamesdmanton.bsky.social · 29/09/2026

For now there are sources and binaries for Windows, Mac and Linux, along with a universal ImageJ plugin. Napari is an obvious next target for support, but I'd like to know what you'd want developed. Both HDF5 and Zarr support are in the works.

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James Manton @jamesdmanton.bsky.social · 29/09/2026

Blosc2 bitshuffle + Zstd-5 beats us on speed (approximately double encode and decode), but produces files about a third larger. Nevertheless, if speed is the ultimate concern, this is probably the way to go.

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James Manton @jamesdmanton.bsky.social · 29/09/2026

A key design goal was to exceed the bandwidth of a saturated sCMOS camera (0.7813 GiB/s) without needing a GPU. Current benchmarking suggests my office PC should be able to handle 3. Another goal was high compression ratio: JPEG-XL lossless (effort 9) beats us by 3.7%, but we're ~1000× faster.

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James Manton @jamesdmanton.bsky.social · 29/09/2026

I've been working on a fast, high-ratio image compressor to try and alleviate the data storage issues myself and some of my colleagues have recently been facing. Before I 'release' version 1, it'd be great to gain some feedback regarding performance and missing features. github.com/jdmanton/rad...

github.com

GitHub - jdmanton/radelta

Contribute to jdmanton/radelta development by creating an account on GitHub.

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Nils Norlin @nilsnorlin.bsky.social · 17/09/2026

I am looking for postdoc candidates for two opportunities in my lab at Lund University. 1. Co-application for a two-year postdoc scholarship on method development in 3D spatial biology, with applications in lung physiology, cancer and neuroscience.

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Stephen McLaughlin @lmbbiophysics.bsky.social · 08/09/2026

Registration is closing tomorrow, 9th September, for our 10th Next Generation Biophysics Symposium. Join us either in-person or on-line by clicking here: www3.mrc-lmb.cam.ac.uk/sites/nextge...

A card with information on the Next Generation Biophysics Symposium on 16th September 2026 at the LMB. Registration is closing 9th September. A QR code link to registration website.

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Lara Krüger @lara-kruger.bsky.social · 09/06/2026

📢 We are looking for a Junior Group Leader to join us at @institutcurie.bsky.social! Having joined the department just over a year ago, I can honestly say that it is an exceptionally stimulating and supportive scientific environment, filled with outstanding colleagues — all in the heart of Paris.

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MRC Laboratory of Molecular Biology @mrclmb.ac.uk · 25/08/2026

Looking to solve complex, technical challenges across hardware, software and large-scale computing systems? Join our Scientific Computing team and use open-source software and custom-built systems to support the LMB's computing infrastructure. Closes 17 SEP Read more: www.jobs.ac.uk/job/DSR455/s...

MRC Laboratory of Molecular Biology hiring Scientific Computing Officer to support breakthrough discoveries with complex computing tasks.

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Heilemann Lab @heilemannlab.bsky.social · 17/08/2026

🚨 2x PhD opportunities: single-molecule/super-resolution microscopy & image analysis of membrane proteins 🔬(DM for details) 👉🏻 tinyurl.com/5dt7ncby 👉🏻 tinyurl.com/5e52dth2 🙏 Dear colleagues & friends, pls distribute - Thank you! 🙏 @crc1507.bsky.social imol.uni-frankfurt.de @goetheuni.bsky.social

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James Manton @jamesdmanton.bsky.social · 11/08/2026

GCHQ strikes again and deems knowledge of our new approach to tissue clearing too dangerous for public consumption! We're still working on the information included on the website, so hopefully we're unblocked by the time we've finished. If you never hear from me again you know what's happened...

A web warning from the National Cyber Security Centre, a part of GCHQ, stating:

"This site may be associated with malicious activity or malware.

Access to this site has been blocked by the Protective DNS Service

Site: replicaclearing.org

Please contact your local Network Administrator or IT support if you require further assistance"

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Anh Hoang Le, PhD 🏳️‍🌈🏴󠁧󠁢󠁳󠁣󠁴󠁿🇻🇳 @anhhle2702.bsky.social · 27/07/2026

Yey, I figured out how to display 3D movie stacks in #ChimeraX, thanks to @dabiophysicist.bsky.social for the suggestion. My original tiff was not ome-tiff so you'll need to convert it first (do this with #Python), then adjust voxelsize in ChimeraX so the image isn't flat, record, and voila!

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Kevin Dean @kevin-dean.bsky.social · 16/07/2026

New preprint! Using multiscale ExM/OPM/ASLM, we show that oncogenic drivers leave distinct 3D architectural fingerprints in intact liver tissue: NRAS primarily remodels cell shape, whereas CTNNB1 shifts mitochondrial architecture toward a pericentral-like state. tinyurl.com/kepy33m6

biorxiv.org

Deciphering the Multiscale Morphology of Somatic Oncogenic Alterations in Hepatocellular Carcinoma

Somatic oncogenic mutations are typically defined by their molecular alterations, yet how they reorganize cellular architecture within intact tissues remain largely unknown. Here, we demonstrate that ...

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MRC Laboratory of Molecular Biology @mrclmb.ac.uk · 26/06/2026

2026 marks the tenth edition of the Next Generation Biophysics Symposium! Registration for this year’s event, happening at the LMB on Wednesday 16th September, is open now ➡️ www3.mrc-lmb.cam.ac.uk/sites/nextge…

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James Manton @jamesdmanton.bsky.social · 25/06/2026

Thanks! The calibration gave @miguelcmestre.bsky.social a bit of a headache (thanks to some interference from other components), but once that was done it was surprisingly trivial to get nicely reconstructed images out using our code.

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James Manton @jamesdmanton.bsky.social · 25/06/2026

To achieve this, we integrated a beam shifting device into the optical path and acquired four frames for every slice of the z stack. Between frames, the image is shifted by half a pixel in a 2×2 xy grid. Then, a simple algorithm based on the Richardson–Lucy iteration reconstructs the full image.

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James Manton @jamesdmanton.bsky.social · 25/06/2026

We've updated our cleared-tissue direct-view oblique plane microscopy preprint to include our latest resolution-enhancing results. Now the Nyquist sampling of our camera is no longer a limitation and so we obtain a diffraction-limited 2 μm lateral resolution! www.biorxiv.org/content/10.6...

An panel of three images showing 1) raw data, 2) bicubic interpolated data on a two-fold finer grid, 3) properly upsampled data on a two-fold finer grid, for two parallel neuronal filaments that can only be resolved as separate entities in the upsampled image.

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Adam Bowman @adam-bowman.bsky.social · 09/06/2026

Excited to share our first lab preprint! We enabled fast wide-field FLIM with low noise and high dynamic range. We built compact resonant modules for EO-FLIM that fit into your hand and developed methods to capture multi-exponential phasor plots at up to 500 Hz. www.biorxiv.org/content/10.6...

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Biohub @biohub.org · 11/06/2026

In a series of 3 papers and preprints, we’re thrilled to share with you the working laser phase plate. In collaboration with research led by Holger Müller at UC Berkeley, this is a huge innovation in imaging to make small and faint objects inside cells visible. bit.ly/4vK9LVn

Waves of laser light coming from four different directions and meeting in the middle brightly inside the cavity of the laser phase plate

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James Manton @jamesdmanton.bsky.social · 11/06/2026

Are you sure it's a C-mount lens and not CS-mount? There's a 5 mm difference in flange distance, which would cause quite a focal shift.

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Sandrine Lévêque Fort 🔬 @slfort.bsky.social · 05/06/2026

🔬 Happy to share our new paper showing that fluorophore brightness open a new dimension in SMLM microscopy ! Thanks to all authors @laurent-le.bsky.social S. K. Sreenivas @emmanuelfort.bsky.social ! @ismolab.bsky.social @instlangevin.bsky.social @cnrs.fr rdcu.be/fmIeD doi.org/10.1038/s415...

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Loïc A. Royer 💻🔬🧪 @loicaroyer.bsky.social · 03/06/2026

Want to build some of the most advanced light-sheet microscopes in the world to watch life assemble itself cell by cell? The Royer Lab @ Biohub is hiring an Optical Engineer (Advanced Light Sheet Microscopy). 🧪🔬💻🔧 #Hardware + #Python + Advanced #Optics job-boards.greenhouse.io/biohub/jobs/...

job-boards.greenhouse.io

Optical Engineer, Advanced Light Sheet Microscopy

San Francisco, CA (Hybrid)

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Ali Shaib @alishaib.bsky.social · 01/06/2026

Hello #world, meet 1,000× Expansion Microscopy. A small gel would grow to the size of an Olympic swimming pool, while amino-acid-scale distances become visible with ordinary light microscopy. Led by Helena Hu from @eboyden3.bsky.social's lab, in collab with us. Story: www.biorxiv.org/content/10.6...

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Karl Deisseroth @deisseroth.bsky.social · 01/06/2026

Directional elements: the preprints are out! 1/n Congratulations to our amazing team: biorxiv.org/content/10.6... biorxiv.org/content/10.6... biorxiv.org/content/10.6... We screened for principles governing global brain dynamics by developing a set of new methods: 1) conformal immersion microscopy;

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Michael Lin, MD PhD @michaelzlin.bsky.social · 02/06/2026

Excited to announce big steps for electrical imaging in the brain! In 4 preprints, we and collaborators present 2 new GFP-based voltage sensors: ASAP6c for high-throughput spike recordings, and ASAP7y for subthreshold 1P and 2P imaging bit.ly/4x3k3kX bit.ly/3RKZhq3 bit.ly/4o4fKl3 bit.ly/4uHXuk3 🧵

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James Manton @jamesdmanton.bsky.social · 02/06/2026

Fortunately, GCHQ didn't block the bioRxiv submission of the related manuscript! bsky.app/profile/jame...

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James Manton @jamesdmanton.bsky.social · 02/06/2026

We anticipate that this implementation of direct-view oblique plane microscopy will provide both a practical platform for volumetric cleared-tissue imaging and an extensible basis for further improvements in imaging performance. If you'd like to give it a try please contact me and we can host you!

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James Manton @jamesdmanton.bsky.social · 02/06/2026

Our exemplar system cost less than 40 k€ and can be assembled in less than a day. We have provided open-source hardware and software at www.ctdvopm.org, along with an interactive CAD render and full parts list.

Screenshot of 'hardware' page of www.ctdvopm.org showing interactive CAD render and the start of the parts list.

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James Manton @jamesdmanton.bsky.social · 02/06/2026

ExM is great for clearing tissues, but the 64-fold (or larger!) volume increase prohibits imaging some samples, even with our extended FOV. So, we also developed our own tissue clearing method (REPLICA), with water as the index-matching liquid, which will soon be fully described in its own preprint.

A maximum intensity projection of a REPLICA-cleared kidney slice, immunostained for aquaporin 2 (cyan) and CD105 (magenta).

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James Manton @jamesdmanton.bsky.social · 02/06/2026

As well as producing samples ourselves, we worked with friends and colleagues from the LMB and Imperial College London to put the system through its paces, imaging samples cleared with iDISCO (n = 1.56), MACS/ECi (n = 1.56), Ce3D (n = 1.50), OptiMuS-prime (n = 1.49) and ExM (n = 1.33).

A gallery of cleared tissue images, including an iDISCO-cleared hairy chimpanzee skin organoid, a MACS-cleared mouse lung, an ECi-cleared mouse gut and an OptiMuS-prime-cleared mouse brain.

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James Manton @jamesdmanton.bsky.social · 02/06/2026

Through a careful reanalysis of the optical theory of remote refocussing, we realised that the detection system could be unaltered over the range n = 1.33–1.56, as diffraction-limited imaging performance is maintained. Only the processing needs to change, to account for a slight volume compression.

$Plot of Strehl ratio as a function of depth, showing that a value greater than 0.8 is maintained for at least 18 mm for refractive indices in the range 1.33 to 1.56.$

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James Manton @jamesdmanton.bsky.social · 02/06/2026

Furthermore, by careful use of optomechanics and 3D printed parts, the detection system is inherently alignment-free, drastically simplifying construction. The light sheet launch is similarly simple, with changes in refractive index requiring only the insertion of a chock to change incidence angle.

$Zoomed CAD render showing chock for a refractive index of 1.45.$

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James Manton @jamesdmanton.bsky.social · 02/06/2026

Compared with the closest magnification microscope objective (Olympus 1.25× 0.04 NA), we maintain the same FOV but increase resolution more than three-fold. Alternatively, compared with the closest resolution microscope objective (Nikon 4× 0.13 NA) we obtain an almost eight-fold larger imaging area.

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James Manton @jamesdmanton.bsky.social · 02/06/2026

While existing OPM systems can be tricky to align due to their multiple objective lenses and relay systems, our CtDvOPM instrument uses a single detection lens. By using a commercially available bi-telecentric lens (designed for parts inspection), we boost field-of-view while maintaining resolution.

Illustrative schematic and CAD render of CtDvOPM system.

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James Manton @jamesdmanton.bsky.social · 02/06/2026

CtDvOPM can image conventionally-mounted expanded, aqueous or non-aqueous cleared tissue samples at up to 2 μm lateral by 14 μm axial resolution over a 10 mm × 10 mm × 25 mm sample volume without image tiling, at up to 400 million voxels per second.

Maximum intensity projection of a mouse female reproductive tract labelled for PGP9.5.

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James Manton @jamesdmanton.bsky.social · 02/06/2026

We introduce cleared-tissue direct-view oblique plane microscopy (CtDvOPM), which enables optically sectioned subcellular resolution imaging of centimetre-scale tissues at high-throughput over the full range of clearing media refractive indices (n = 1.33–1.56).

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James Manton @jamesdmanton.bsky.social · 02/06/2026

We present: Index-agnostic oblique plane light sheet microscopy of centimetre-scale cleared tissues at subcellular resolution www.biorxiv.org/content/10.6...

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James Manton @jamesdmanton.bsky.social · 01/06/2026

It's not clear if this is because GCHQ thinks our new microscope "is the bomb", a "cleared and well-presented danger" or because, as microscopists, we "look after the small things and [so] the big ones will take care of themselves".

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James Manton @jamesdmanton.bsky.social · 01/06/2026

It's not every day you set up a new website and have it blocked by the Government Communications Headquarters (GCHQ), an intelligence service so secretive the UK government didn't formally acknowledge its existence until 1994, 75 years after it was founded...

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