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

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...

A day in the life of a growing hiPSC spheroid expressing endogenously mStayGold-tagged histone 3.3 for #FluorescenceFriday and the #Snouty aficionados. 28 hours (and >50,000 exposures) later and they are still going! Home-brewed volume projection.

#HappyMicroscopyMonday #microscopycommunity - Join the BINA Builders for a panel and discussion on the shift from proprietary systems to community-driven innovation. Thursday, May 21! Learn more: buff.ly/pMShl9t

Altair Direct View OPM Preprint! We built a simplified direct-view oblique-plane microscope for imaging big, optically accessible specimens with a single-objective light-sheet geometry. Delivers... • ~5.4 mm field of view • ~2.6 μm, ~3.4 μm, and ~17.8 μm resolution in X/Y/Z

We invented “triplet tumbling microscopy” (TTM) to track protein-protein interactions in living cells! Tag your protein with GFP and see it interact with *untagged* binding partners www.biorxiv.org/content/10.6...

We’re hiring a scientist to work on microscopy at Calico! If you’re excited about developing and applying cutting edge microscopy to a variety of biological questions, we’d love to hear from you. Find more information and apply here: www.calicolabs.com/careers/?gh_...

What if you got to work with some of your best friends on a science project? I can't publish how fun this was, but I can show you the data (🧵)! Last week, we posted our second neutrophil swarming paper to bioRxiv and I wanted to post my favorite videos here~ www.biorxiv.org/content/10.6...

Snouty objectives enable high resolution light-sheet microscopy with standard microscope platforms and sample formats! -> Here are citable repositories with CAD, Zemax and summarized optomechanical specifications: AMS_AGY_v3: a.k.a. Empress Snout, now the best! github.com/amsikking/AM...

@patrickzager.bsky.social acquired this lovely 3D timelapse of live neutrophil membrane protrusions on the snoutscope at the UCSF Center for Advanced Light Microscopy. Shown are three orthogonal maximum intensity projections.

Hi microscopy folks! I'm looking for your advice 💡 We're shopping for cyclic immunofluorescence instruments to increase throughput and multiplex-ability of tissue IF. Have you worked with cyclic IF platforms (Comet, CellScape, Cell DIVE)? Thoughts? Pain points? Alternatives to consider? Thanks!

The power of CAD! The ability to precisely draw 3D objects and have them made is still a miracle to me! -> Here's an old design for an alloy block to hold microcentrifuge tubes near freezing when moving them around. It's simple, but I wouldn't want to draw it or make it by hand...

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "Z" scientist! (26/26) -> "Z" is for Zebra, Zucchini, and...Zernike? en.wikipedia.org/wiki/Frits_Z... Art by @annesikking.bsky.social (my Mum).

Proof of principle. A critical step in many projects... -> Here's the first data from an AMS-AGY objective. Without building the whole instrument, it showed that a tilted Snouty (Frustum) objective can avoid the resolution lost in an oblique plane microscope! amsikking.github.io/high_na_sing...

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "Y" scientist! (25/26) -> "Y" is for Yak, Yam, and...Young? en.wikipedia.org/wiki/Thomas_... Art by @annesikking.bsky.social (my Mum).

Our snouty v3 (AMS-AGY v3) objective arrived today! Looking forward to getting it installed on our single objective light sheet system very soon...

How has AI changed CAD? Can AI now reliably generate 3D parts, assemblies and drawings? I'm interested to hear about new tools, workflows and experiences ;) -> Here's a series of enclosures I designed years ago for housing custom lab equipment. Can AI CAD just generate this automatically now?

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "X" scientist! (24/26) -> "X" is for Xeme, Xigua, and...Xanthopoulos? en.wikipedia.org/wiki/Basilis... Art by @annesikking.bsky.social (my Mum).

Sharing: A simple automatic liquid dispense arrangement (SALDA) for timelapse microscopy. -> A SALDA enables accurate and repeatable liquid perturbations during timelapse microscopy and avoids environmental disturbance and vibrations from the user! Details here: amsikking.github.io/SALDA_for_ti...

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "W" scientist! (23/26) -> "W" is for Worm, Watercress, and...Watt? en.wikipedia.org/wiki/James_W... Art by @annesikking.bsky.social (my Mum).

Pro tip! As much as I like the 55deg #Snouty microscope configuration (previous post) it's hard to align and keep aligned! -> Consider using pre-designed O2-O3 optomechanics and an eyepiece to help avoid collisions during the set up! github.com/amsikking/SO...

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "V" scientist! (22/26) -> "V" is for Viper, Vanilla, and...Volta? en.wikipedia.org/wiki/Alessan... Art by @annesikking.bsky.social (my Mum).

I'm excited to be hiring an intern to develop new fluorescence-based assays for alpha synuclein aggregation at Calico during summer 2026 😃 🔬 If you're a current PhD student who loves microscopy, unnatural amino acids, and/or synuclein biophysics, please apply! www.calicolabs.com/careers/?gh_...

The ASI machine shop made a nice replica model of the AMS-AGY v3 objective for us to have in the #CellBio2025 booth. The first of the real ones will be ready by the end of the year.

Hands down my favorite #Snouty microscope configuration! -> The air objective with a 55deg light-sheet. It's not the highest resolution version, but the convenience of the air objective, the large field of view and the steep sectioning of the light-sheet make it a pleasure to use! #AIRR #miOPM

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "U" scientist! (21/26) -> "U" is for Unicorn, Ugli, and...Umov? en.wikipedia.org/wiki/Nikolay... Art by @annesikking.bsky.social (my Mum).

Fast, gentle, 3D and high resolution makes miOPM ideal for timelapse microscopy of complex neural networks! -> Here's a unique iNeuron-iAstrocyte coculture imaged by github.com/gav-sturm and carefully prepared by @kunalshroff.bsky.social from the @kampmann.bsky.social lab. doi.org/10.1101/2025...

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "T" scientist! (20/26) -> "T" is for Tarantula, Turnip, and...Taylor? en.wikipedia.org/wiki/Brook_T... Art by @annesikking.bsky.social (my Mum).

Has anyone had this problem? A hydrophobic water objective? The objective is great but we struggle to keep the water on the lens... -> Maybe a solution is to paint a circle around the nose with a 'hydrophobic barrier pap pen" (link below). Has anyone tried this? www.fishersci.com/shop/product...

Another huge advantage of miOPM is that it's gentle! A light-sheet microscope that's compatible with standard slides and multi-well plates! -> Here we show 3D mitochondrial membrane potential in mammalian cells (GFP/RFP for mito, Cy5 for DNA). The cells move around freely! doi.org/10.1101/2025...

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "S" scientist! (19/26) -> "S" is for Squirrel, Strawberry, and...Snell? en.wikipedia.org/wiki/Willebr... Art by @annesikking.bsky.social (my Mum).

A huge advantage of miOPM is 3D imaging with an air objective (previous post), but for extra depth you can also use a water objective! -> Here's mouse alveolar organoids with Muc1 AT2 cells (green), TOM20 mitochondria (blue), RAGE AT1 cells (gray) and DAPI (magenta). doi.org/10.1101/2025...

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "R" scientist! (18/26) -> "R" is for Rabbit, Radish, and...Raman? en.wikipedia.org/wiki/C._V._R... Art by @annesikking.bsky.social (my Mum).

The future of High-Content Imaging has arrived. -> Ultra-fast 3D imaging of multi-well plates at high resolution using an air objective! See previous posts and the new miOPM preprint for details: doi.org/10.1101/2025...

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "Q" scientist! (17/26) -> "Q" is for Quail, Quince, and...Quinn? en.wikipedia.org/wiki/Helen_Q... Art by @annesikking.bsky.social (my Mum).

Playing around with how to represent volume in #Snouty light sheet data. Here is a dividing hiPSC with endogenously tagged histone in all three orthogonal projections. Bluer is further away. If anything, it distracts from politics.

We present multi-immersion Oblique Plane microscope (miOPM), a light-sheet platform that can be adapted to a wide range of applications, from sensitive live cell imaging to imaging organs and cleared tissues. www.biorxiv.org/content/10.1...

The culmination of many years work. One of the most advanced light-sheet microscopes in the world! -> A large field of view Snouty light-sheet microscope, with any immersion remote refocus and real-time multi-angle projections! For details see previous posts and here: github.com/amsikking/HT...

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "P" scientist! (16/26) -> "P" is for Pelican, Pineapple, and...Planck? en.wikipedia.org/wiki/Max_Pla... Art by @annesikking.bsky.social (my Mum).

@tanner-fadero.bsky.social told me there was a discussion about the unofficial name for #snouty V3. We have had Mr. Snouty and King Snouty, and there were people suggesting Emperor Snouty. I think it is time for a Lady or EMPRESS snouty. I have created Art to support this.

What if we could get good 3D imaging in 'any' sample refractive index? Previously we showed how remote refocus optics can get good 3D imaging in a 'watery' sample (RI=1.33) with any immersion objective. -> Here we show how a zoom lens can adjust remote refocus optics to any sample refractive index!

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "O" scientist! (15/26) -> "O" is for Octopus, Orange, and...Ohm? en.wikipedia.org/wiki/Georg_Ohm Art by @annesikking.bsky.social (my Mum).

Thrilled to share our new work in Cell Reports Methods: MCT-ASLM, a multiscale light-sheet microscopy platform that captures biology from tissue landscapes down to organelles, revealing rare events like sparse neurons and micrometastases. www.cell.com/cell-reports...

What if we could use 'any' immersion objective and get good 3D imaging? Normally we can't as we must refractive index match the immersion to the sample (previous post). -> However, I realized a few years ago that we can get good 3D imaging with any immersion using remote refocus optics!

Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "N" scientist! (14/26) -> "N" is for Narwhal, Nasturtium, and...Newton? en.wikipedia.org/wiki/Isaac_N... Art by @annesikking.bsky.social (my Mum).

Some first raw (not deskewed) data of live human induced pluripotent stem cells from #Snouty now ready for some serious live imaging. Light sheet moving at a 38-degree angle through the cell layer; coverslip is on the bottom.

Bluesky is now the platform of choice for the scientific community. From @jenlucpiquant.bsky.social on @arstechnica.com arstechnica.com/science/2025...

👀 What if your flow cytometer could see the invisible? Our new preprint introduces single-molecule flow cytometry (smFC), pushing detection sensitivity 10–80× beyond conventional flow cytometry. www.biorxiv.org/content/10.1...

Why use water or oil immersion objectives instead of air? 1) The higher refractive index (RI) ups the numerical aperture and can improve resolution. 2) It can greatly improve 3D imaging! -> Here we show how 'standard focus' only works well if the RI of the immersion matches the RI of the sample.

How many photons are in a GFP? — more than last year, and more than you thought. Here's a simple, cheap, and practical method to break a fundamental limit in fluorescence microscopy. But it only works in light sheet!