Alfred Millett-Sikking
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amsikking.bsky.social
Alfred Millett-Sikking
@amsikking.bsky.social
I'm a Physicist and R&D Engineer. Fascinated by optimal designs, I seek to improve and invent technologies.

Homepage: amsikking.github.io
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...
November 24, 2025 at 12:34 AM
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).
November 23, 2025 at 11:38 PM
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...
November 12, 2025 at 12:56 AM
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...
November 9, 2025 at 8:03 PM
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).
November 9, 2025 at 7:26 PM
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...
October 26, 2025 at 5:15 PM
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).
October 26, 2025 at 4:48 PM
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...
October 13, 2025 at 12:44 AM
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).
October 13, 2025 at 12:08 AM
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...
September 28, 2025 at 6:33 PM
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).
September 28, 2025 at 5:59 PM
So whereas normally we arrange remote refocus optics as a series of static lenses that are optimized for a particular sample RI (e.g. 1.51 for oily samples).

-> Here we show a zoom lens design that can dynamically adjust to any sample refractive index from water to oil! (i.e. RI range 1.33-1.51)
September 14, 2025 at 11:20 PM
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!
September 14, 2025 at 11:20 PM
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).
September 14, 2025 at 5:56 PM
The different immersion options have different advantages.

-> Here I show that (with a watery sample) the water objective can image the deepest, the oil objective has the highest numerical aperture and the air objective avoids liquid immersion!
September 1, 2025 at 6:20 PM
This enables new and interesting imaging regimes with totally mismatched immersion and sample refractive index!

-> Here I show a remote refocus microscope imaging deep into a watery sample. The water immersion works well (as expected), but so does the air and oil immersion!
September 1, 2025 at 6:20 PM
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!
September 1, 2025 at 6:20 PM
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).
September 1, 2025 at 6:13 PM
In practice it looks something like this...
August 25, 2025 at 3:25 AM
If we don’t RI match the immersion/sample then the images get blurry as we use standard focus look deeper into the sample (especially at high numerical aperture).

-> Here we show how spherical aberration increases dramatically as an air objective attempts to image deeper into a watery sample.
August 25, 2025 at 3:25 AM
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.
August 25, 2025 at 3:25 AM
In practice it looks something like this...
August 25, 2025 at 2:48 AM
If we don't RI match the immersion/sample then the images get blurry as we look deeper into the sample with standard focus (especially at high numerical aperture).

-> Here we show the effect, where spherical aberration increases dramatically as an air objective attempts to image deep into water.
August 25, 2025 at 2:48 AM
Before inventing Any Immersion Remote Refocus (AIRR) microscopy, which enables air objectives to image deep into liquids, I tried other ways to alleviate the immersion problem...

-> He's an objective 'hat' I designed to wick oil towards the sample for multi-well plate imaging. AIRR is better!
August 18, 2025 at 4:55 AM
Celebrating science with art! Every 2 weeks for 1 year, the full alphabet. Like, reply or repost with your favorite "M" scientist!

(13/26) -> "M" is for Mouse, Mandarin, Mango and...Maxwell?

en.wikipedia.org/wiki/James_C...

Art by @annesikking.bsky.social (my Mum).
August 18, 2025 at 4:49 AM