Weight says a lot. In the kitchen, it could mean cooking with too little or too much of an ingredient. For scientists, a molecule鈥檚 weight can help determine its makeup. This, in turn, can shed light on whether a potential drug is acting on the body or not working at all. Weight can even reveal what tumors are made of, potentially influencing treatment options. For measures like this and more, researchers turn to a technique called mass spectrometry.
鈥淎 mass spectrometer is essentially a very precise scale,鈥� says 黑料吃瓜资源 (CSHL) Research Associate Professor Paolo Cifani. 鈥淚magine a bucket full of different molecules. Using mass spectrometry, you can figure out what molecules and how many are in that bucket. This enables researchers to try to answer questions like, 鈥楢re there different proteins, lipids, or other small molecules in one tumor versus another?鈥欌��
Now, Cifani and his team at CSHL鈥檚 Mass Spectrometry facility have developed a new technique to push the performance of their instruments. Their innovation may improve drug target discovery while helping scientists answer long-standing questions about human health and biology.
When trying to identify molecules in complex mixtures, mass spectrometer sensitivity was thought to be determined almost exclusively by speed. Typical scans involve transferring molecules to a gaseous state. Their ions are then measured in sequence by taking 鈥渟napshots鈥� inside the 鈥渂ucket鈥� every few seconds. However, if too many ions accumulate, they can start interacting, which messes up the scan. So, 鈥渋t seems intuitive that the faster you go, the more you can sequence,鈥� Cifani says.
鈥淪peed is always a factor,鈥� he explains. 鈥淏ut potentially interesting molecules can be overlooked because they鈥檙e not seen in the snapshot, as the spectrometer gets 鈥榖linded鈥� by more abundant ions. Our new technique looks to remedy that.鈥�
Cifani likens it to a sorting system. Rather than measuring everything in the chamber at once, the Cifani lab breaks scans down into 鈥渂ins.鈥� If there鈥檚 a molecule at much higher levels, it only fills one bin, not the others.
鈥淥ur method is much better at measuring differences in concentration,鈥� he says. 鈥淭hat鈥檚 very important when studying a drug versus a placebo.鈥�
The lab is now working to refine and expand access to their new technique. Sharing it in the journal Analytical Chemistry is an important first step. Many CSHL core facilities offer technical expertise not only to researchers at the Laboratory but also to other institutions. Cifani and his team are confident their technique will be valuable to the scientific community. 鈥淭his is a proof of concept,鈥� he says. 鈥淲e鈥檙e ready to inspire discovery, worldwide.鈥�
Written by: Nick Wurm, Communications Specialist | [email protected] | 516-367-5940
Funding
CSHL/Northwell Health Affiliation, Simons Foundation
Citation
Panepinto, M.C.,听et al., 鈥�High Dynamic Range Peptide Mass听Spectrometry听Using听Segmented听Precursor Ion Accumulation鈥�,听Analytical Chemistry,听October 15. 2025.听DOI:听
Core Facilites
鈥淭丑别 Mass Spectrometry Core Facility provides state-of-the-art quantitative analysis of proteins and peptides, protein-protein interactions, and post-translational modifications. The resource also offers the ability to detect lipids, metabolites, and other small molecules. The facility supports experimental design, sample preparation, LC-MS analyses, and data analysis and interpretation.鈥� 鈥� Director Paolo Cifani, Ph.D.