Andrew G. York

Ahhhh that makes sense, the halfway point sucks.

In my experience, the hardest part of teaching a biologist to code is uninstalling the three extra versions of python they have on their Mac (brew, conda, etc), and relearning basic crap that Mac obfuscates like "file paths".

I've never failed, when I try this. I've done it on Windows and Linux. I don't do anything fancy, I follow the default instructions. What goes wrong for you?

This press release is bizarre. We've had the iSIM and the SoRa as commercial products for almost a decade now.

How can you ignore a technique that's widely distributed and strictly superior? Do you just not know about it?

cc @tanner-fadero.bsky.social

That's why we use the alignment crane: thousands of dollars worth of 3d precision that detaches post-alignment, leaving only a solid steel post/clamp that's nearly incapable of drift.

A. Structure of AsLOV2 PDB~2V1A (Halavaty, 2007) with mutations resulting in MagLOV~2 highlighted. Spin transitions driven by radio-frequency (RF) fields in the presence of a static magnetic field are optically detected via fluorescence measurements on an otherwise standard widefield microscope. Similar effects have recently been observed in other protein systems (Burd 2025, Meng 2025, Feder 2025). B. Simplified photocycle diagram in the case of a large external magnetic field. C. A single cell expressing MagLOV 2 displaying an MFE of ~50% (measured as a change in fluorescence intensity in the presence of an applied field). For MFE measurements, the magnetic field was switched between 0 mT and 10 mT. D. Black dots: data from a single cell expressing MagLOV 2 displaying an ODMR signal with ~10% contrast. The static field B_0 is ~21.6 mT. Blue line (shade): the mean (std) of all single cell data in a field of view (~1000 cells). E. The static magnetic field B_0 was varied by adjusting the magnet's position, and ODMR spectra recorded. Red-lines are Lorentzian fits. Blue line is a theoretical prediction (i.e. is not a fit) of the expected resonance frequency of an electron spin with $\bar\gamma_e$=28 MHz/mT.

Electronics, radio electronics, optical parts, and an animal sized MRI coil are assembled to perform fluorescence MRI measurements using MagLOV.

MagLOV quantum sensing update! Much improved imaging (>10% single cell ODMR contrast), detailed characterisation and simulation, and new experimental demonstrations taking us a step closer to applications.
www.biorxiv.org/content/10.1...

SI: www.biorxiv.org/content/10.1...

I think my speakers aren't working, I can't hear the Benny Hill music?

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!

Oh I think I get it - 10 fps acquisition, 250 fps playback?

What a great answer! That's way more photons than I would have guessed.

More photons than Alexa 647! Amazing.

(also, looks like 10 fps, not 250, right?)

There's about 10^5 photons in a single GFP [1]; how many do we estimate are in a single smURFP?

(I'm interested if smURFP is really more photostable than GFP, vs the smURFP cell here is just more densely tagged and imaged at a lower excitation rate)

[1] doi.org/10.1016/j.bb...

Very lucky to be at UCSF with such great microscopy facilities. These instruments are definitely pushing the limits of what we thought feasible in live imaging! Excited to keep exploring how these single cells organize and secrete such precise morphologies.

comparison table for v2 and v3

Production has started for a new #Snoutscope objective, AMS-AGY v3. It has significantly larger FOV and some other tweaks from v1 and v2. Currently accepting pre-orders. The price will need to increase modestly after deliveries start late October.

I got a text from Yovan Bodal, who just used our #snoutscope @UCSF to image fly embryos. His quote says it all!

"This was the best results we've gotten on any instrument, possibly for the least amount of work on my end. Here's a GIF of individual mRNAs coming off the gene as they get transcribed:"

It will also have enormous advantages over light field, because it will be several orders of magnitude faster, and much higher resolution.

Light field is an inherently slow, low resolution technique, unfortunately. It's strange no one seems to notice this.

I know exactly how to do that inference. Hit me up for a zoom call.

(It's the same math as every other inverse problem in microscopy, btw).

Hey awesome!

How many pixels are in it?

(I know we both know this, but I'm hoping folks will stop using the correct but shibboleth-y terms "etendue"/"space-bandwidth product" and switch to using the more accessible term "how many pixels are in that lens")

doi.org/10.5281/zeno...

HIGH-RESOLUTION IN VIVO BRAIN IMAGING OF DROSOPHILA 🪰
New Preprint by Tassara et al.!

www.biorxiv.org/content/10.1...
#FluorescenceMonday #SnoutClub 1/6

Near-infrared co-illumination of fluorescent proteins reduces photobleaching and phototoxicity - Nature Biotechnology A dual illumination method reduces photobleaching for green and yellow fluorescent proteins.

Illumination gives singlets and triplets in ~100-1 ratio. Bleaching is mostly from the long-lived (~ms) reactive triplet. Triplets also absorb light, which can be protective or destructive depending on the color and FP. Higher intensity gives more triplet absorption.

www.nature.com/articles/s41...

I recommend these optomechanics for 'O2-O3' in a single-objective light-sheet (SOLS) microscope:
-> Mechanically and thermally stable.
-> Relatively straightforward to align.
-> 10 popular configurations.

Make your own:

github.com/amsikking/SO...

Or buy it from @jsdaniel02.bsky.social at ASI!

Who else has a #Snouty objective? I currently have 25 members in #SnoutClub! But I think there's a LOT MORE out there... Anyone else care to join?

-> Just reply here with a pic of your #Snouty and I'll add you!

Why? It helps us promote and develop the technology!

amsikking.github.io/snoutclub/

The hosts are friends of mine, it'll be at their place. It's a very tech-focused house with a lot of very driven people living (and working?) there.

Click the link and register to get the address.

RSVP to Lecture night with Andrew York | Partiful Gather round the fire and make new friends! Andrew is a physicist at Calico and recently co-discovered magnetic responsivity in fluorescent proteins. It’s one of my favorite discoveries because it’s ...

I'll be telling stories about science tonight in San Francisco. Come through!

partiful.com/e/ldwWPLR2fO...

The real draw is the crew hosting me, though. The local biotech hacker/maker/entrepreneur scene is PACKED with brilliant, inspiring folks.

No slides, just stories.

This is such a fun project! I love the kind of work that F.R.O.s attack.

Resolution doubling in live, multicellular organisms via multifocal structured illumination microscopy - Nature Methods Structured illumination using multifocal patterned illumination via a digital micromirror device integrated into a conventional wide-field microscope, followed by digital processing, allows resolution...

Is the DeepSIM an MSIM descendant? How did you like it?

www.nature.com/articles/nme...

Oh cool! Glad to hear it's useful :⁠-⁠)

I have never regretted trying to help a young person.