Our Stories

Seeing deeper into plasma

Since acquiring the Orbitrap Astral MS, Ralf said a large part of his lab’s work has focused on plasma proteomics in partnership with numerous external collaborators from academia and the biopharmaceutical industry.

With earlier-generation mass spectrometers, Ralf said his lab could quantify a maximum of 1,000 proteins from plasma, a fraction of the plasma proteome, leaving many lower-abundance, biologically informative proteins beyond reach. Using the Orbitrap Astral MS, he said they can reach around 2,000 with the same sample preparation techniques. When they combine Orbitrap Astral MS with technologies that separate and enrich low-abundance proteins, the scientists can see as many as 8,000 proteins, giving them a far richer molecular picture of what is happening in the samples they analyze, he said.  

The point, Ralf said, is not simply that the instrument produces a bigger number. The added coverage, he said, can help researchers detect molecular changes they might otherwise miss and prioritize which changes deserve closer follow-up.

In one research project, the Monash team analyzed plasma from a healthy control group and compared it to plasma samples collected from COVID-19 patients or trauma patients who had been admitted to an intensive care unit.  The researchers said they quantified about 7,000 proteins and identified those at much higher levels in samples from COVID-19 and trauma patients. Ralf said the team also observed unique protein expression patterns associated with disease severity and patient outcomes. In another study, the Monash team analyzed plasma from colorectal cancer patients who relapsed after treatment and those who did not. The research revealed distinct protein patterns, called protein signatures, differentiating the two groups, Ralf said.

 The ability to observe thousands more proteins using the Orbitrap Astral MS helped the researchers identify which disease pathways may be altered and why some patients fare worse than others, Ralf said. That information can help guide further research into potential new drug or vaccine targets, he said.

“If somebody had told me three, four years ago that we will be able to identify 8,000 proteins from plasma, I would have considered it impossible. And, you know, here we are. Achieving this level is a significant milestone for the field,” Ralf said.

Cell by cell

Plasma is not the only place where deeper insights into protein changes are reshaping research. Orbitrap Astral MS’s depth of view, specificity, and speed of analysis have enabled the Monash lab to probe the proteins of individual cells more deeply, Ralf said.

With previous technology, there simply wasn’t enough sensitivity to comprehensively analyze proteins in a single cell, Ralf said. And proteins cannot be amplified, meaning a tiny amount cannot be copied to boost the protein signal.

The workaround that many labs used was “bulk proteomics,” Ralf said. Instead of analyzing one cell at a time, Ralf’s team would combine roughly a million cells and extract enough protein from the pool for the mass spectrometer. The problem, he noted, is that tissues like cancers are highly heterogeneous – a mix of tumor cells, cancer stem cells, surrounding healthy cells, and infiltrating immune cells – so the final readout is an average that hides what makes any one cell different.

Advances in high-sensitivity mass spectrometry now allow researchers to measure hundreds to thousands of proteins from extremely small samples, making it possible to study individual cells rather than averaged mixtures.

“What we can do now, and this is enabled in particular by mass spectrometers like the Orbitrap Astral MS, is analyze the protein content of individual cells,” Ralf said. “We don’t have to create averages anymore. We can look at the protein content of individual cells and see, for example, what makes one cell cancerous while the neighboring cell remains healthy.”

That single-cell view uncovered in research labs such as Monash can help drug developers connect protein changes to specific cell states, generate hypotheses about disease mechanisms, and identify where further diagnostic or therapeutic research may be warranted, he said.

A broader view of biology

Taken together, Monash University’s research in plasma and single-cell proteomics points to the same conclusion: the value of deeper coverage is not simply that researchers can report more proteins. It is that they can move beyond dominant signals and pooled averages to see biology with greater clarity—in plasma, where low-abundance proteins may reveal important disease-associated changes, and in individual cells, where critical differences are often lost in bulk measurements.

For Ralf and his collaborators, that broader view is changing how proteomics can contribute to the translation of scientific research into new therapies and diagnostics. With more informative data and faster analysis, researchers can sharpen the questions they ask, prioritize which findings warrant closer follow-up, and investigate disease biology at a level previously difficult to reach.

 “There is so much that we don’t know,” Ralf said. “The Orbitrap Astral MS gives us deeper coverage, more information, and more proteins to play with, to target, to develop drugs. That’s what it enables.”