The new study, published in the Proceedings of the National Academy of Sciences, was led by Mahdiyeh Shahi, a former graduate student at Purdue who is now a clinical chemistry postdoctoral fellow at the University of Minnesota Medical School, together with R. Graham Cooks, the Henry Bohn Hass Distinguished Professor of Chemistry in Purdue’s James Tarpo Jr. and Margaret Tarpo Department of Chemistry. The pair collaborated with Dr. Alfredo Quiñones-Hinojosa, a professor of neurosurgery at the Mayo Clinic in Jacksonville, Florida, along with his postdoctoral fellow Loizos Michaelides and other Mayo colleagues, to develop and test a mass spectrometry method designed specifically for the constraints of the operating room. The work draws on an analytical tradition that Cooks himself helped launch more than two decades ago.

Mass spectrometry, at its core, is a way of weighing molecules. The technique ionizes chemical compounds and measures their mass-to-charge ratios, allowing researchers to identify and quantify the complex mixture of metabolites, lipids, and other molecules present in a sample. In a clinical context, that molecular fingerprint can reveal things that conventional microscopy cannot: whether tissue is cancerous, which subtype of tumor it belongs to, and even which genetic mutations the tumor carries. The obstacle has always been speed and practicality. Traditional mass spectrometry requires extensive sample preparation, vacuum systems, and lengthy analysis, none of which fits a surgical workflow in which decisions must be made in minutes.

The Purdue method sidesteps those constraints through ambient ionization, an approach invented at Purdue and first described in 2004. Instead of preparing samples inside sealed vacuum chambers, ambient ionization creates ions from molecules in the open environment, permitting molecular measurements to be made essentially in place. The technique has since been commercialized and widely adopted. The specific variant used in the new study, called syringe touch spray, is strikingly simple: an ordinary hypodermic needle takes a sample from the patient, and the needle itself becomes the ionization source for the mass spectrometric analysis. No elaborate extraction, no separate sampling step, no fundamental redesign of surgical practice.

In the study, the researchers analyzed 86 human brain samples obtained through MRI-guided precision surgery at the Mayo Clinic. During such operations, a small number of samples are taken from surgeon-defined positions in the brain for pathological examination. The team transferred fractions of those samples onto the plunger of a hypodermic needle and sprayed a solution that enabled measurement of the ratio of signals for multiple pairs of endogenous compounds in the brain, using tandem mass spectrometry. The entire measurement took roughly three minutes. Rather than hunting for a single biomarker, the method relies on ratiomics: comparing the relative abundance of pairs of metabolites that naturally occur in brain tissue, which proved far more robust than absolute concentrations that can vary with sample handling.

The results were unambiguous. Ratios of endogenous metabolites distinguished glioma from non-tumor tissue with high confidence, and the same measurements classified tumor subtypes and mutation status, information that normally requires days of laboratory work after surgery. Cooks emphasized that the simple ambient ionization approach enables fast, clinically compatible analysis with the potential to improve margin assessment and enhance patient outcomes. Because glioma cells spread into nearby healthy brain tissue, particularly at the tumor margins, they are notoriously difficult to detect with the conventional technologies available in the operating room. Tissue left behind after surgery can seed recurrence and make subsequent treatment more difficult, so every improvement in margin detection carries direct consequences for survival.

Shahi stressed that the molecular information produced by the technique is simply not available under current standard-of-care procedures. If the diagnostic method were approved for clinical use, she explained, it would provide actionable molecular information during surgery, on a time scale compatible with the operation itself, whereas current pathology results arrive only after hours. That information could directly influence treatment, including the extent of tumor resection, although the final surgical decision would rest with the surgeon weighing the overall clinical context rather than the mass spectrometry results alone. She also noted that the molecular profiles could help guide the selection of targeted therapies, extending the technique’s value beyond the operating room into treatment planning.

Importantly, the researchers are careful to position the technology as an addition to, not a replacement for, existing practice. Cooks noted that the technology would not displace the current standard of care during brain tumor surgery. Instead, it could provide surgeons with molecular information that is not currently available in the operating room, helping to guide decisions during tumor removal, particularly at the tumor margins where the stakes are highest. In previous work published in PNAS in 2024, the team’s measurements were made in the hospital during surgery; in the new study, mass spectrometry data were recorded remotely and compared against the available clinical information, demonstrating that a very simple and quick measurement can carry high discriminating power between diseased and non-diseased tissue while also providing information on tumor grade and mutation status.

The research team included Shahi and Cooks along with Quiñones-Hinojosa; Michaelides; Diogo Moniz Garcia, a former Mayo Clinic postdoctoral fellow now a neurosurgery resident at Washington University in St. Louis; and Aleeshba N. Basil of the Mayo Clinic. Kenneth Lane Virgin of Indiana University School of Medicine, previously affiliated with Purdue’s Aston Laboratories for Mass Spectrometry, also contributed. Shahi and Cooks are members of the Purdue Institute for Cancer Research and work in the Analytical Chemistry group in Purdue’s College of Science. The work was supported by the National Institutes of Health, including the National Cancer Institute’s Innovative Molecular Analysis Technologies Program and the National Center for Advancing Translational Sciences, along with corporate support from Waters Corporation. Specimens came from the Mayo Clinic Florida Neurosurgery BRIDGE Biobank, a central nervous system bioresource built on patient-derived samples.

With the 86-sample study complete, the team’s next step is a similar study involving more than 50 patients in which the technique is used during surgery itself, which Cooks says would pave the way for a clinical trial to be proposed. If those trials succeed, the three-minute molecular readout could become a routine companion to the surgeon’s eye and the pathologist’s microscope, turning one of neurosurgery’s most persistent blind spots into measurable, actionable data at the precise moment it matters most.

Subject of Research: Rapid intraoperative mass spectrometry metabolite ratiomics for glioma margin diagnosis and classification during brain surgery

Article Title: Mass spectrometry offers faster look at the edges of brain tumors

Article References: Mass spectrometry offers faster look at the edges of brain tumors. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: glioma, mass spectrometry, brain tumor margins, ambient ionization, syringe touch spray, tumor resection, metabolite ratiomics, intraoperative diagnostics, Purdue University, Mayo Clinic, PNAS, targeted therapy

A new study led by Candice Bedford, a research scientist in Purdue University’s Department of Earth, Atmospheric, and Planetary Sciences, and published in Communications Earth & Environment, shows that the Margin Unit did not record a single lakeshore environment. Instead, the rocks preserve a layered history of multiple, distinct episodes in which water of different origins and temperatures moved through, altered, and reworked the crust. Groundwater percolated through fractures and left carbonate deposits behind. Lake water or evolving groundwater systems chemically transformed minerals that had formed earlier. And in a final act, warm hydrothermal fluids pushed through the fractured bedrock, depositing vein minerals that recorded yet another chapter in the crater’s watery past. The Margin Unit, the team concluded, became a kind of crossroads where several aqueous systems converged over geological time.

Bedford and an international team of collaborators pieced together this history using measurements and images from Perseverance, particularly the data returned by the rover’s SuperCam instrument. SuperCam, mounted on the rover’s mast or head, combines remote chemical analysis techniques, including laser-induced breakdown spectroscopy, with high-resolution imaging, allowing scientists to determine the composition of rocks and individual mineral grains from a distance. That capability proved essential on the Margin Unit, where the crucial evidence was written at scales invisible from orbit: fine fractures, thin mineral veins, and subtle chemical variations between grains that together revealed a sequence of water-rock interactions spanning a long stretch of Martian history.

“If there is one thing I have learned after 10 years working with Mars rovers, it is that Mars constantly throws surprises at you,” Bedford said. “It is very rare that things are as we expect them to be from orbital data. They are usually far more complex and interesting, which is what makes planetary exploration so exciting.” Her comment captures a recurring lesson of the Mars 2020 mission: orbital spectroscopy can flag promising locations, but only close-up, grain-scale analysis can reveal the true sequence of geological events preserved in the rocks.

The oldest chapter of the story begins deep underground. At higher elevations within the Margin Unit, Perseverance encountered coarse, crystalline rocks rich in olivine, an iron-magnesium silicate mineral commonly associated with igneous processes. The chemistry and texture of these olivine-bearing rocks suggest that they originally formed from a magma that cooled slowly beneath the Martian surface, allowing large crystals to grow. In other words, the foundation of the Margin Unit is not sediment laid down on a lakebed but volcanic rock crystallized in the crust, later exposed and made available for alteration by whatever water arrived afterward. This igneous starting point matters, because it gives scientists a well-defined baseline against which every subsequent chemical change introduced by water can be measured.

The first watery episode left an unmistakable signature at lower elevations. The team identified carbonate-rich ridges cutting across the bedrock, evidence that groundwater once traveled through a network of fractures and precipitated minerals along its path. Bedford offered an analogy drawn from terrestrial plumbing: “The fractures are like pipes, and the carbonate is the Mars ‘limescale’ that eventually blocked the ‘pipes’ up.” Just as hard water leaves mineral scale inside household pipes, the Martian groundwater left carbonate crusts inside its fracture conduits, gradually sealing them. These carbonate fills record the chemistry of the fluids that deposited them and, by extension, the subsurface environment of early Mars, making them prime targets in the search for conditions that could once have supported microbial life.

The story did not end with the groundwater. The rover also found widespread silica distributed through the lower-elevation rocks, along with clear evidence that previously formed carbonates had been chemically altered. That combination points to a second, later episode of water-rock interaction, one that may have involved water from Jezero’s ancient lake spilling into the margin rocks or shifts in the groundwater system itself changing the composition and flow paths of subsurface fluids. Either way, the alteration of the earlier carbonates demonstrates that the region’s water history was not a single event but a sequence of overlapping processes, each overprinting and modifying the record left by the last.

The final chapter is perhaps the most surprising. Perseverance discovered a mineral vein containing fluorite and calcium sulfate, a chemical pairing that points to a hydrothermal episode occurring after the groundwater and lake-related alteration had already taken place. Fluorite, the mineral form of calcium fluoride, typically precipitates from warm, chemically distinctive fluids, and its presence alongside calcium sulfate suggests that heated waters moved through the fractured bedrock late in the crater’s history. Hydrothermal systems are of special interest to astrobiologists because on Earth they support thriving ecosystems independent of sunlight, making similar environments on Mars compelling places to look for signs of past life. The vein indicates that even after Jezero’s lake had faded from the scene, the crust beneath it remained geologically and hydrologically active.

Taken together, the findings fundamentally reshape how scientists view the Margin Unit and, by extension, the history of water in Jezero Crater and across Mars. “Before we arrived at the Margin Unit, the main hypothesis was that these carbonates formed from interaction with the lake that existed in Jezero Crater, but now we know that this location became a sort of crossroads for aqueous systems, which significantly altered the crystalline volcanic rocks that were originally there,” Bedford said. Environments where water and rock interact repeatedly over long periods are precisely the kinds of settings that intrigue scientists studying the possibility of life on Mars, because such systems can supply energy and chemical gradients that living organisms can exploit. The Margin Unit had long been considered a promising research target since orbiting spacecraft first detected its strong carbonate signatures, but only Perseverance’s close-up view could reveal the fractures, mineral veins, and individual grains that exposed its far more complex history.

The research drew on the collective expertise of the SuperCam team, which Roger Wiens, professor of Earth, Atmospheric, and Planetary Sciences at Purdue, has led since before the launch of NASA’s Mars 2020 mission. Briony Horgan, professor of planetary science at Purdue, contributed to the work and served as campaign science lead during Perseverance’s exploration of the Margin Unit, and former Purdue doctoral students Stephanie Connell and Brad Garczynski also played important roles. Bedford, Wiens, and Connell received support from NASA for the SuperCam instrument. During its traverse, Perseverance collected rock samples from the Margin Unit, sealing them in tubes for a future mission intended to carry them to Earth. In terrestrial laboratories, those samples will be analyzed with instruments far more sensitive than anything a rover can carry, allowing scientists to examine the environments recorded in the rocks at microscopic scales and to assess their potential to preserve signs of ancient habitability.

“I hope this work helps to reshape how scientists view the history of water in Jezero Crater and across Mars,” Bedford said. “Ultimately, I hope this study helps planetary scientists reconstruct the changing climate and habitability of early Mars and provides helpful context for future researchers when these cached Perseverance samples are returned to Earth to be analyzed for potential biosignatures.” The paper, titled “Lake- and groundwater-associated alteration of the olivine-rich Margin Unit in Jezero Crater, Mars,” was accepted for publication in Communications Earth & Environment. For now, the findings stand as a vivid reminder that planetary surfaces keep their secrets at scales that only surface missions can reach, and that the red planet’s ancient waters were not a single still lake but a dynamic, evolving system whose shifting flows left an intricate, overlapping archive in the rocks along Jezero’s rim.

Subject of Research: Alteration of the olivine-rich Margin Unit in Jezero Crater, Mars, by groundwater, lake water, and hydrothermal fluids as observed by the Perseverance rover

Article Title: Purdue-led study finds an ancient history of water on Mars that shifted over time

Article References: Purdue-led study finds an ancient history of water on Mars that shifted over time. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: Mars, Perseverance rover, Jezero Crater, Margin Unit, carbonates, groundwater, hydrothermal activity, SuperCam, olivine, astrobiology, water-rock interaction, Purdue University