James Manton
jamesdmanton.bsky.social
James Manton
@jamesdmanton.bsky.social
Applied physicist & microscopist/microscopologist
We've now discovered some neat cell culture dishes that feature a 50 micron thick film of a proprietary polymer with refractive index even closer to water than FEP. They work just as well as our homemade FEP assembly and are available in multiwell plate format too!

www.sarstedt.com/en/products/...
October 28, 2025 at 8:27 PM
We present a simple method to easily increase the imageable depth of an expansion microscopy gel on a typical inverted microscope ten-fold, using some carefully placed FEP film and a water dipping objective lens:
September 15, 2025 at 8:42 AM
Thanks to a dose of activation energy from @dpshepherd.bsky.social, I've finally cleaned up my Biggs–Andrews accelerated version of our automatic parameter-free deconvolution code and made it available at beryl.mrc-lmb.cam.ac.uk/rlgcba_noteb.... This is ~2.75× faster than the previous version.

1/4
May 9, 2025 at 7:08 PM
Thanks to some CUDA trickery*, our automatic parameter-free deconvolution code is now ~3× faster than the previous version (~9× faster than the original) while still producing exactly the same results as before.

Try it out for free using Google Colab at beryl.mrc-lmb.cam.ac.uk/rlgc_notebook/

1 / 2
May 6, 2025 at 7:35 PM
Then, we use our new direct-view oblique plane microscope (doi.org/10.1364/OPTI...) to image a 4× expanded brain organoid with 5-fold undersampling. While the new algorithm is slower than the previous approach, it avoids artefacts and produces denoised or deconvolved volumes simultaneously.

[6/8]
May 2, 2025 at 2:22 PM
Next, we apply the algorithm to high-resolution OPM data, looking at diffraction-limited clathrin puncta in a single cell. As expected, the algorithm outperforms bicubic interpolation and, most importantly, correctly fails when the undersampling factor is too large.

[5/8]
May 2, 2025 at 2:22 PM
First, we introduce the principle and show that it works via simulations.

[4/8]
May 2, 2025 at 2:22 PM
It feels a bit strange having such a watery liquid behave optically like glass...

www.biorxiv.org/content/10.1...
March 12, 2025 at 3:19 PM
As a proof-of-concept, Jacob Lamb built a direct-view mesoscopic OPM using a €700 Ximea MU196MR-ON camera with 1.4 μm pixels. We could then image expanded cerebral organoids, created by @miguelcmestre.bsky.social, with a 2 μm × 2 μm × 22 μm resolution over a 5.3 mm × 2.88 mm field of view.
February 12, 2025 at 4:41 PM
In our work, we just put the camera directly into the remote refocus volume to detect the oblique plane directly, without the need for a tertiary microscope system!
February 12, 2025 at 4:41 PM
Hoffmann et al. have also shown how an image transfer fibre plate can be used to achieve a similar goal without the photon losses of diffractive elements, but this requires a costly custom-made optical element.

doi.org/10.1038/s414...
February 12, 2025 at 4:41 PM
More recent work, e.g. by Shao et al. and Daetwyler et al., have extended this concept, but the relatively low photon efficiency and difficult alignment procedure remain.

doi.org/10.1364/OPTI...
doi.org/10.1364/OPTI...
February 12, 2025 at 4:41 PM
In 2019, Hoffmann and Judkewitz showed that a diffraction grating could be used to redirect the light into the tertiary objective, but this led to a distorted point spread function and low photon efficiency.

doi.org/10.1364/OPTI...
February 12, 2025 at 4:41 PM
This leads to all the light collected by the primary objective and directed into the remote refocussing volume by the secondary objective missing the entrance aperture of the tertiary objective! Over the past few years, a number of groups have proposed neat solutions to this problem.
February 12, 2025 at 4:41 PM
Our automatic parameter-free deconvolution code is now 2–3× faster while still producing exactly the same results as before. If you want to try it out, we have a Google Notebook implementation available at beryl.mrc-lmb.cam.ac.uk/rlgc_notebook/. Manuscript WIP.
January 22, 2025 at 10:45 AM
As of this evening, our office currently has 74.65 megapixels of display real estate, which should keep us going for a while. Almost half of that (33.18 megapixels) is provided by my new 8K screen (Dell UP3218K), which is absolutely fantastic.

That's a full-chip Prime 95B image at 100 %...
December 9, 2024 at 10:37 PM
We've been imaging larger and larger samples recently, which means more and more pixels to display. What better way to do that than with 3× 43" 4K displays?

Three grown men for scale.

(More seriously, these will be instrument control screens, but we couldn't resist trying them in the office first)
December 9, 2024 at 10:37 PM
We've recently updated our multispectral microscopy manuscript to clarify a few points (particularly regarding SNR) and add eight supplementary figures. Courtesy of Sjoerd Stallinga, we now also have a derivation of the appropriate Cramér–Rao lower bound!

www.biorxiv.org/content/10.1...
November 27, 2024 at 6:11 PM
There's just over a fortnight left to apply to the LMB's PhD programme, which features a veritable smörgåsbord of projects (including one of our own on engineering the next generation of fluorescent proteins for live and super-resolution microscopy).

www2.mrc-lmb.cam.ac.uk/students/int...
November 17, 2024 at 7:39 PM
And if we try milling some flat glass, we see interesting undulations in the milled surface. If any of us ever form a band, we all thought this would make a good album cover.

8/8
November 16, 2024 at 9:43 AM
We also see nice contrast with the tiny gold wires that connect the sensor chip to the main board. The ion beam showed good contrast over most of the board, which gives us confidence that it'll be a good tool for inspecting chips after some semi-destructive modification.

7/8
November 16, 2024 at 9:35 AM
If we repeat the process, but offset the milling by a fraction of a pixel, we see a different cut through the electronics.

6/8
November 16, 2024 at 9:28 AM
Yep, definitely electronics.

5/8
November 16, 2024 at 9:20 AM
Rotating the view by ~90 degrees shows some interesting structures, which are presumably to do with the electronics of the chip.

4/8
November 16, 2024 at 9:12 AM
"I wonder if we mill a trench if we'll see anything interesting underneath..."

We've definitely made a hole, but it's not clear that we've learnt anything. Maybe if we rotate the view we'll see something.

3/8
November 16, 2024 at 9:05 AM