Raphael Jorand, PhD


Instruments and Projects

Raphael Jorand, PhD. I build scientific instruments and help people use them. This page shows the machines and projects behind my CV, from a cell-injection robot in 2009 to the microscopes I built during my PhD. Work I did for my current employer is described only briefly, because most of it is not mine to show.


A robot that injects living cells into microfluidic chips (Leiden, 2009)

During a six-month Erasmus internship at the Leiden Institute of Chemistry (Leiden University, the Netherlands), I worked on lab automation for microfluidics. The goal was to show that a robot could connect to a microfluidic chip and inject living cells into its channels without a person doing it by hand.

Top view of a robot arm with an injection needle positioned over a microfluidic chip, Leiden University, 2009
The robot, seen from above, with the injection needle over the chip holder.
  • I wrote the program that controlled the robot, in Python, with a graphical interface.
  • I built a control and calibration system to get the best positioning out of the robot.
  • I cultured HeLa cells and injected them into the chips, then measured the results from video with ImageJ.
  • By the end, the automated injection of living cells into microfluidic channels worked, and the lab used the results to present its connection technology to life-science companies.
Screenshot of the Python program with a graphical interface that controlled the injection robot
The control software I wrote for the robot.

The robot at work

Ten injections in a row into the same well, to test how repeatable the positioning was:

A close-up of one injection:

An injection with two needles:


Light-sheet microscopes for tumor spheroids (Toulouse, 2010–2013)

For my PhD at ITAV (CNRS, Toulouse), I worked on imaging tumor spheroids: balls of cancer cells a few hundred micrometres across, used to test drugs. A light-sheet microscope (also called SPIM) lights the sample with a thin sheet of laser light from the side and takes a picture of that one slice, then the next, until the whole sample is recorded in 3D. I built several of them.

The first one: a light sheet built from parts

The first microscope was a plain light sheet, assembled from individual lenses, stages and a camera at a time when you could not easily buy one. It became the routine instrument for imaging spheroids in the lab.

A compact home-built light-sheet microscope on an optical table at ITAV, Toulouse
The first light-sheet microscope on the optical table.
3D drawing of the home-built light-sheet microscope on its optical table
My drawing of the same microscope, made for the user guide.
A thin sheet of laser light crossing the water-filled sample chamber of the microscope
The light sheet crossing the sample chamber.

Adding adaptive optics

Spheroids are thick and they bend light, so images get blurry deep inside. To fix that, I built a second, larger microscope with a closed-loop adaptive optics system: a wavefront sensor measures how the sample distorts the light, and a deformable mirror corrects it.

Top view of the light-sheet microscope with adaptive optics on its optical table at ITAV, Toulouse
The adaptive-optics microscope, seen from above.
Side view of the adaptive-optics light-sheet microscope: lenses, mirrors, deformable mirror and cameras on an optical table
The same microscope during assembly.

The work was published in 2012 and, to my knowledge, was the first published light-sheet microscope with closed-loop adaptive optics: Jorand R. et al., “Deep and clear optical imaging of thick inhomogeneous samples”, PLOS ONE, 2012 (co-first author).

Optical layout of the light-sheet microscope with the wavefront sensor and deformable mirror, from the PLOS ONE 2012 paper
How it is laid out: the wavefront sensor and the deformable mirror sit on the detection path.
Images of a tumor spheroid with and without adaptive optics correction, from the PLOS ONE 2012 paper
The same spheroid without and with the correction.

Both figures are from Jorand R, Le Corre G, Andilla J, et al. (2012), PLOS ONE 7(4): e35795, doi.org/10.1371/journal.pone.0035795, published under a CC BY licence.

What they see

A tumor spheroid scanned plane by plane:

The planes put back together in 3D:

A multimodal light sheet at ICFO (Barcelona, 2012)

As a visiting researcher at ICFO, I worked on a light-sheet microscope that could switch between one-photon and two-photon excitation, Gaussian and Bessel beams, and cylindrical-lens or scanned light sheets. Flip mirrors and a sliding lens let us change from one mode to another in very little time, so we could compare the methods on the same thick samples. The comparison was presented at the ELMI meeting in 2013 and published as “Imaging tissue-mimic with light sheet microscopy: a comparative guideline”, Scientific Reports, 2017 (co-first author).

Diagram of the multimodal light-sheet microscope at ICFO with flip mirrors, axicon, scanner and cylindrical lens, and images of the five beam types
My diagram of the ICFO microscope (labels in French). Top: flip mirrors M1 to M4 choose the laser colour and the way the sheet is made. Bottom: the five kinds of light sheet it could produce.

Label-free light scattering with ONERA (2012)

With ONERA, the French aerospace lab, we tested one of their optical methods on our tumor spheroids: measuring how the spheroids scatter light across colours, polarizations and angles, without any fluorescent label. The first results were presented at a SPIE conference in 2012 (“Hyperspectral polarized light scattering to study tumor cells in in-vitro samples”, Rivière, Ceolato, Lorenzo, Jorand, Ducommun).

One patch per microscope

Each light-sheet microscope I worked on got its own mission patch, which I drew myself.

Hand-drawn round patch for the SPIM 1 microscope: a light sheet crossing a spheroid
Hand-drawn round patch for the SPIM 2 microscope: satellites and the letters AO, for adaptive optics
Hand-drawn round patch for the SPIM 3 microscope: two objectives, a spheroid and a wavefront map
Hand-drawn round patch for the SPIM 4 microscope, with Spanish and French flags

A light-sheet microscope built from available parts (Bogotá, 2013)

In August 2013 I went to the Universidad de Los Andes in Bogotá for a French–Colombian project on ocean acidification. The biologists there needed to image the tiny calcium structures of sea cucumbers in 3D. We built a light-sheet microscope with what was available, including a UV laser bought on eBay, and I taught the students to assemble it, align it, prepare samples and analyse the images. By the end they were running it themselves.

Light-sheet microscope assembled on an optical table at Universidad de Los Andes, Bogotá
The microscope we built in Bogotá.
Transparent sample chamber with the imaging objective, part of the microscope built in Bogotá
Its sample chamber.

One of the sea-cucumber structures (a sclerite), imaged in 3D on that microscope:


Counting single molecules in cancer cells (City of Hope, 2013–2016)

As a postdoctoral researcher at City of Hope (Duarte, California), I used super-resolution microscopy to look at single receptors on cancer cells: how they group together, and how antibodies and drugs change that. I labeled antibodies, built capture surfaces and wrote analysis methods. Two papers came out of it:

  • “Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer”, Molecular Biology of the Cell, 2016 (co-first author).
  • “Using quantitative single molecule localization microscopy to optimize multivalent HER2-targeting ligands”, Frontiers in Medicine, 2023 (co-first author).

Ten years at ONI (2016–today)

I joined Oxford Nanoimaging (ONI) in 2016 as its seventh employee and helped take the Nanoimager, a benchtop super-resolution microscope, from prototype to product. Since then I have built and led its field application team, installed more than 100 systems around the world, trained hundreds of scientists, and worked on product launches, quality and customer support. More recently I designed and built AI assistants for our customers and our own team.

Writing about quality

Setting up quality checks for instruments made me read a lot about how quality systems and regulators work. I wrote two short primers on it: The Fire That Never Started, on quality, and The Mirror, on FDA approval.

Contact

You can reach me through the contact page or on LinkedIn.