#pokolenieNCN – Maciej Trusiak: We hold the world record in lensless tomography

The NCN Generation is made up of researchers whose work pushes the boundaries of knowledge and changes our lives – improving health, protecting the environment, advancing technology and deepening our understanding of the world. The protagonist of episode 5 is Maciej Trusiak, who builds lensless microscopes that can image hundreds of thousands of cells in a single frame. Thanks to them, it is possible to check, immediately after a sample is collected, whether a biopsy is suitable for further analysis.

Maciej Trusiak is a professor at the Faculty of Mechatronics of the Warsaw University of Technology, where he leads the computational imaging group. As he himself emphasises, from the very beginning he was driven to “ask his own questions, follow his own path, and pursue his own goals, plans and dreams”. He started out on his own, and today he leads a team of 15. His research is funded by NCN and the European Research Council.

A simple device with a concrete application

An oncological diagnosis often begins with the collection of a small sample – cells or tissue – for example a thyroid smear. A histopathologist assesses it only after the slide has been stained, which takes time, and sometimes it turns out that the material was collected incorrectly and the biopsy has to be repeated.

The lensless microscope developed by Maciej Trusiak’s team makes it possible to check the quality of the specimen immediately after collection, before it goes on for further processing. This makes it possible to detect more quickly that a biopsy needs to be repeated, sparing the patient valuable time. As the researcher emphasises, the device will not replace the histopathologist, but it can become a tool for their preliminary assessment. The first research units are already being installed in the laboratories of biologists and physicians. Implementing a clinical version requires a manufacturing partner and – as the researcher himself estimates – several years of work. The design itself is, moreover, very inexpensive: the camera costs around one hundred dollars, the light source is an LED, and the sample is placed on an ordinary glass slide.

A hologram instead of a lens

A classical microscope magnifies the image using a system of lenses, and the drawback of such a solution is the small field of view – only a few cells can be observed at a time. In lensless microscopy there are no lenses. The sample lies directly above the camera sensor and is illuminated by a beam of light which – passing through the thin specimen – undergoes slight scattering. The undisturbed wave and the wave disturbed by the sample overlap and form a hologram on the sensor array. The image is produced only at a second stage, numerically: an algorithm reverses the propagation of the light and reconstructs the structure of the sample.

Such an arrangement makes it possible to image an entire cell culture – tens, or even hundreds of thousands, of cells at once. This increases the chance of capturing significant phenomena and reduces the risk of drawing erroneous conclusions on the basis of a fragment. The lensless microscope also copes with transparent samples, which do not absorb light and remain invisible to a classical camera. For this purpose it uses phase contrast – a mechanism described in the 1930s by Frits Zernike (Nobel Prize in Physics in 1953). Different intracellular structures – the nucleus, mitochondria, the cytoskeleton – delay the passing light wave to varying degrees, and reconstructing these delays makes it possible to distinguish them within the cell without the need to stain it.

A world record in lensless tomography

Lensless microscopy is currently being developed at many centres around the world – in the United States, China, Germany and the Netherlands. The common goal is to obtain as much information as possible from a single measurement: a wide field of view, a large measurement volume and high contrast when imaging transparent samples. A particular challenge remains tomography, that is, three-dimensional imaging.

The previous world record belonged to the team of Prof. Aydogan Ozcan from UCLA, who imaged a slice of mouse brain 200 micrometres thick. The team from the Warsaw University of Technology has pushed this limit to 500 micrometres, taking into account the phenomenon of multiple light scattering and numerically reversing it. The paper describing this result has been accepted for publication in the journal Light: Science & Applications.

Selected quotes

An advantage over the classical microscope

Classical microscopes allow you to image five to ten cells, which means we have a field of view at least ten thousand times larger. I like to think that this gives us two advantages. Firstly, we increase the probability that we will see something interesting, because we image all the cells. And the second thing is that we lower the probability that we will make some kind of error. If we look only at a fragment of a larger whole, we can very easily form a false impression and misjudge the situation.

Application in diagnostics

The best application that comes to my mind is to assist in diagnostics. (…) We take a smear, for example from the thyroid, we have a sample prepared for examination, but we do not know whether it is diagnostic. The histopathologist first has to stain it, look at it, and may then say that the biopsy was collected incorrectly. And we, before all this happens and we lose valuable time – especially for oncology patients – can quickly check whether the specimen was collected properly.

It begins with curiosity

(…) research on lizard venom led to a change in the treatment of diabetes and in human weight loss. It did not begin with the production of medicines at all. Curiosity is absolutely the most important thing, and it is at the start of every discovery. To realise that curiosity, funding is needed. The National Science Centre is essentially the only body in Poland that funds such research. It is very good that it exists – I would like the NCN budget to be at least doubled.

What does NCN mean for researchers?

I have been using funding from the National Science Centre since PRELUDIUM, which my mentor, Professor Krzysztof Patorski, helped me to write. The OPUS and SONATA grants were an absolute foundation that enabled me to apply for an ERC grant at all. I managed to secure it thanks to the experience I had previously gained by delivering NCN grants and building a team. Independence comes from funding – without NCN’s programmes I would not be in science.