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Breaking New Ground in Single-Cell Lipidomics

Collection of red cells with purple nuclei.
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Single-cell lipidomics is emerging as a key area of research, providing unparalleled insight into cellular processes by analyzing the lipid composition of individual cells. Despite offering distinct advantages over traditional bulk lipidomics, single-cell lipidomics also presents unique technical challenges.

In a study published in Analytical Chemistry, researchers from the University of Surrey used Yokogawa’s Single Cellome™ System SS2000 to isolate single cells while preserving their natural lipid profiles – marking a significant breakthrough in the field.

Technology Networks
spoke with Gilberto Barcellos, SS2000 product specialist at Yokogawa, and Dr. Melanie Bailey, professor of analytical science at the University of Surrey, to discuss the growing interest in single-cell lipidomics, the key challenges researchers face and how the SS2000 is helping to overcome these hurdles.

Anna MacDonald (AM):

Why is there so much interest in single-cell lipidomics?


Gilberto Barcellos (GB):
There is a growing interest in the field of single-cell lipidomics because it has the potential to access biological information that has been completely inaccessible thus far with the analytical technologies researchers have had at their disposal. 

For those who are not familiar, lipids are organic compounds that can be found in most living cells, and “lipidomics” is the study of large sets of lipids – single-cell lipidomics, specifically, is the study of all lipids present in a single cell. Lipidomics in bulk, as opposed to lipidomics at the single-cell level, has been around since the early 2000s and it has contributed tremendously to our understanding of biological processes – as it turns out, lipids are an essential part of many processes that happen in living cells and, as such, are an essential part of life. 

However, because lipidomics in bulk examines many cells at the same time, researchers had not been able to visualize the differences between the lipid profiles of specific cells, only to compute the average lipid profiles of many cells. Now, with emerging technologies that can isolate single cells, such as the SS2000, and analytical tools that are more sensitive than ever, this single-cell granularity is possible.


Melanie Bailey, PhD (MB):

We have noted a great deal of interest in single-cell lipidomics from the biosciences community. By developing tools to measure lipids in single cells, or even within sub-cellular compartments, we will be able to understand how cells signal to each other, how cells respond to infection, how cancer develops and make better treatments.  



AM:
What are some of the core challenges researchers currently face when carrying out single-cell lipidomic studies?

GB:
One of the main challenges that researchers who want to do single-cell lipidomics face is  isolating single cells in a way that allows for accurate measurement of lipids. Some of the surrounding concerns include minimizing cell stress and avoiding sample loss.


MB:
The other challenge is finding instrumentation with the requisite sensitivity to detect and identify lipids in single cells. Our work has shown that with careful consideration of sample transfer and background correction, lipids can be detected by the new generation of mass spectrometry instrumentation. 


AM:
Can you tell us about the SS2000 and how it helps to address these issues?

GB:
The SS2000 is a dual microlens spinning disk confocal for live-cell high-content imaging, which can sample single living cells while ensuring the preservation of spatial, morphological and temporal information. It tackles the issue of cell isolation by providing researchers with a tool that can not only sample individual adherent cells for lipidomic analysis without the need for cell suspension, but that can also image these cells in culture, providing users with information about the location of each cell, as well as their morphology and when they were sampled.


MB:
The beauty of this approach is the ability to sample a single-cell – for example a cell infected with a pathogen or expressing a specific marker – and then sample its neighbors. It provides a spatial context not accessible with other techniques.


AM:
The SS2000 was recently used by researchers at the University of Surrey. Can you tell us more about this study and the benefits the system brought?

GB:
The researchers at the University of Surrey have created an innovative workflow using the SS2000 alongside liquid chromatography-mass spectrometry, which is a particularly sensitive analytical technique that can identify and quantify lipids. They have shown that this workflow can identify changes in the lipid profiles of individual cancer cells in response to oxidative stress. 

This is a great step forward for scientists in the field, as it proposes a method to understand how single cells react to different stimuli through changes in their lipidome. The SS2000 plays a pivotal role in this workflow, as it is the tool used to visualize and isolate these cells so that they can be further analyzed individually.


AM:
Are there any other examples of how the system is being utilized that you would like to share? 

GB:
The SS2000 can be used to sample cells not only for mass spectrometry analysis, but also for sequencing applications, in which researchers investigate the transcriptomic content in individual cells. This is exciting because it means that the SS2000 is a tool that, when paired with powerful sample analysis technologies, can extract a very broad range of information from a cell, such as imaging data, mass spectrometry readings and genetic sequences.


MB:
At SEISMIC we are working with users from across the UK to develop and exploit the benefits of the SS2000.  We are working with researchers studying viruses and bacteria, as well as those interested in immunology, synthetic biology and cancer.


AM:
What do you see in store for the future of the single-cell lipidomics field?

MB:

On the mass spectrometry side, we need to improve the sensitivity, selectivity and throughput of single-cell lipidomics so that we can move from tens of cells to hundreds or even thousands of cells per measurement. This will allow us to confidently classify different cellular phenotypes, or better characterize heterogeneity within cell populations.


For further information about the SS2000, please contact Kevin Jan at kevin.jan@yokogawa.com.