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Navigating the Complexities of Single-Cell Research

ARRALYZE glass array with three different shaped wells highlighted. Each well is enlarged to display a different type of cell.
Credit: ARRALYZE
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The advent of single-cell analysis has marked a transformative era in the life sciences, particularly in the field of drug development. This powerful technology allows researchers to dissect the complexities of biological systems at an unprecedented resolution, a single cell at a time. By isolating and examining individual cells, it’s now possible to uncover differences within cell populations that were once masked by averaged data, offering new insights into cellular function, disease mechanisms and drug responses. This level of detail is crucial for the development of more targeted and effective therapeutic strategies.

To delve deeper into the subject, Technology Networks spoke with Dr. Nora Fekete-Drimusz, head of biology at ARRALYZE.

Our discussion focused on three main topics
the transformative impact of single-cell analysis on life science research, the primary challenges researchers face in single-cell analysis and an overview of the company’s multifunctional single-cell platform, CellShepherd®.


Laura Lansdowne (LL): Can you provide an overview of how single-cell analysis is transforming research in the life sciences and its impact on understanding complex biological systems?

 

Nora Fekete-Drimusz (NF-D): In the age of big data, scientists are better equipped to handle a vast amount of information than ever before. They can now collect more data during their experiments, knowing that analyzing it will not pose an issue.


I think this is the main reason why kinetic assays on the single-cell level have been gaining so much traction. We now have the ability to track individual cells throughout the whole duration of the assay (from hours to days). With the help of machine learning, we can get near-instantaneous feedback on the changes occurring in these cells. This becomes important when you are looking at cell populations that are heterogeneous in some aspect. Maybe their affinity to a drug or their ability to recognize and kill another cell type is cell-dependent, these differences would be impossible to pinpoint in experiments that are designed to look at a bulk response.


You could compare it to hiring an engineer from a great university: although you know that the average graduate from that university is highly skilled, the specific abilities and performance of an individual engineer can vary widely. Therefore, evaluating each engineer independently is crucial to understanding their unique strengths and weaknesses, just as assessing individual cells can reveal important variations that are masked when looking at the entire population.

LL: What are the key challenges researchers face in single-cell analysis and how is your technology addressing these challenges?

 

NF-D: One of the most fundamental issues is simply finding your cell of interest in the first place, to be able to track it during the analysis. Providing an environment that has no negative effect on the functionality of the cells would be my second concern. And finally, being limited in how to isolate your best or worst performers is a complaint we also hear a lot from scientists. At ARRALYZE we specifically considered these issues when designing CellShepherd. Using our glass nanowells cells are immobilized in a small, confined area that can be continuously imaged. AI-driven algorithms identify and track the cells, while the inert material and controlled environment ensure that you observe the cells in their true physiological state. Finally, after defining your cells of interest, you can gently and precisely isolate them for any downstream analysis you choose to perform (low volume).

 

LL: Can you describe the core technological advancements that LIDE glass structuring technology brings to microfluidics and how it overcomes the limitations of existing technologies? 

NF-D: I think we can all agree that glass is the choice of material for biological applications, due to its high optical properties, inertness and cost-effectiveness. Unfortunately, traditional glass micromachining methods often introduce stress and micro-defects to its structure, but laser induced deep etching (LIDE) overcomes these issues by enabling the creation of small, high-aspect-ratio features without compromising the integrity of the glass. The digital nature of LIDE means that design changes can be implemented quickly and cost-effectively. It also offers high-throughput production, making it economically viable even for complex designs. One of the standout features of the ARRALYZE technology is its ability to create deep wells that physically immobilize cells, which is particularly beneficial for single-cell screening applications. This level of customization in well shapes and sizes enhances the versatility of glass microfluidic devices, catering to a wide range of assays. In essence, LIDE transforms glass into an ideal material for microfluidics, combining precision, reliability and economic efficiency in a way that hasn’t been available till now.

 

LL: CellShepherd can support researchers working in various areas, including cell therapy, cell line development, synthetic biology and monoclonal antibody production. Can you tell us more about the teams using your product currently?  


NF-D: We now have a network of international research groups working with CellShepherd on two continents. While I can’t disclose their projects before publication, I can safely say that they are our best resource for understanding exactly what the life science community requires from our device. Thanks to the close collaborations, we can adjust functionalities and fine-tune workflows in a way that supports our users the most.  
 

LL: Sustainability seems to be a huge focus of life science, biotech and pharma at the moment. How does ARRALYZE consider environmental sustainability in its product development? 

NF-D: We believe our most significant contribution is the miniaturization of the cell laboratory. The CellShepherd occupies only one square meter of lab space – this can save a lot of resources. Thanks to our innovative glass nanowell dishes and slides, the quantity of chemicals required for each assay is drastically reduced. Additionally, we aim to minimize plastic usage ‒ our dishes reduce plastic consumption by 90% compared to traditional multitier plates.

 

LL: Looking ahead, what new areas of research or applications do you think will emerge as priorities for ARRALYZE? 


NF-D:
Currently, we are witnessing a paradigm shift in drug testing and development, with a focus directed towards the use of primary cells and organoids, and analysis is increasingly reliant on artificial intelligence. We predict that within five years, organoids will become the model of choice for drug development and cancer research due to their immense physiological relevance. The CellShepherd has huge potential in supporting organoid-based workflows. Our goal is to enable a directed method for composing organoids, providing full support for imaging their 3D structures and their isolation. CellShepherd is also exceptionally well-suited for working with primary cell samples, thanks to its ability to handle extremely small volumes and minimize dead volume.

Dr. Nora Fekete-Drimusz was speaking to Laura Elizabeth Lansdowne, Managing Editor for Technology Networks.

About the interviewee:

Dr. Nora Fekete-Drimusz currently serves as head of biology at ARRALYZE (developed by the technology company LPKF Laser & Electronics SE) and has held the position since May 2021. Prior to this, she served briefly as a cell biology scientist at LPKF. Before joining the company, Fekete-Drimusz conducted postdoctoral research at Hannover Medical School.