Mass Spectrometry in Medicine

Vyas Pujari ’26

Over the past few decades, mass spectrometry has emerged as a powerful analytical tool, routinely employed to detect and quantify thousands of biomolecules, including proteins and metabolites. While its primary application has been in the realm of biological research, mass spectrometry also holds significant utility in medicine. Mass spectrometry operates by ionizing molecules, separating them based on mass-to-charge ratio, and detecting the resulting ions, allowing for precise identification and quantification of biomolecules. Its relevance to medicine can be broadly classified into two main categories that will be explored in this article: pathway-specific research relevant to disease conditions, and diagnostics, particularly in biomarker analysis and detection.

The first category involves using mass spectrometry to explore altered biochemical pathways in various diseases. This can be done by identifying and quantifying biomolecules present under specific disease conditions.Metabolomics, the study of metabolites, plays a crucial role in elucidating human diseases by highlighting metabolic differences. For instance, studies conducted by the Rabinowitz lab at Princeton University have demonstrated distinctive metabolic flux between solid tumors and metastatic ones [1]. Similarly, proteomics, which entails the comprehensive examination of all proteins within a biological sample, contributes significantly to our understanding of diseases and potential treatment strategies. Research into diseases like acute myeloid leukemia (AML), for example, benefits from the global proteome profiling techniques developed in renowned laboratories such as the Mann lab at the Max Planck Institute. AML serves as a compelling example of the complexity of cancer treatment, where resistance to targeted therapies necessitates a multifaceted approach to uncover and exploit cancer vulnerabilities [2].

This branch of research, whether directly pinpointing therapeutic targets or indirectly uncovering disease mechanisms, exemplifies the nuanced and multifunctional role of mass spectrometry in advancing medical knowledge and therapeutic interventions. The capacity of mass spectrometry to provide comprehensive insights into the proteomic and metabolic landscape of diseases aids in the continuous search for effective treatments, underscoring its value in both direct and indirect research applications.

In medical diagnosis, there is a growing demand for accurate biomarkers, such as proteins, peptides, lipids, and metabolites, to facilitate early disease diagnosis and improve patient outcomes[4]. Mass spectrometry (MS) not only aids in biomarker discovery but also in their detection in clinical settings, although the latter remains limited.

Proteins, in particular, serve as prominent sources of biomarkers and drug targets in human diseases. Recent technological advancements in MS-based proteomics have enabled the generation of thousands of proteome profiles in a single clinical study. However, challenges such as lack of standardization hinder reproducibility in discoveries. This is why an “untargeted” approach, also known as discovery proteomics, is recommended, allowing for precise quantification and validation, where no prior information about the proteins in the sample is available [3].

Despite efforts in biomarker discovery, only a few protein biomarkers have transitioned into clinical practice. For instance, the FDA-approved OVA1 test for ovarian cancer was identified using MS-based proteomics but developed using immunoassays. Challenges including standardization, validation, and clinical adoption persist, but addressing them could broaden the clinical utilization of MS-based assays, thereby enhancing healthcare delivery and patient outcomes [3]

While most in vitro diagnostics rely on immunoassays, their limitations, such as low sensitivity and limited dynamic range, prompt consideration of alternative approaches [5]. For example, in COVID-19 diagnosis, PCR-based tests offer rapid scalability but lack insights into disease severity. Conventional biomarker assays present deployment challenges, but MS-based proteomics emerges as a promising solution, swiftly delivering clinical and biological information from samples like blood plasma or serum. MS-based proteomics holds significant potential for rapid responses in novel infectious scenarios and has already demonstrated utility in biomarker discovery and profiling in research laboratories [6]

Standardization plays a critical role in both discovering biomarkers and detecting them for diagnosis. It facilitates target verification for the former and ensures robust diagnosis for the latter. However, considerations of throughput and cost are pivotal, especially in the latter aspect [4] The effectiveness of biomarkers in delivering personalized clinical information relies on a reproducible and efficient process for collecting, processing, and analyzing biological samples. Moreover, Mass Spectrometers are both expensive to obtain and operate. There are developments, though, in developing more cost-effective mass spectrometers. The U.S. FDA has approved several MS-based methods for clinical use, yet obstacles remain, including the need for standardized sample handling and analytical procedures, as well as overcoming regulatory and logistical barriers [4]. Studies must provide the knowledge needed for regulatory approvals to have a real chance of making it to clinical practice [2].

Vyas Pujari is a staff writer at The Princeton Medical Review. He can be reached at vp2085@princeton.edu.

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