Simultaneous analysis of numerous low-molecular-weight metabolites in human plasma in less than one second

Biological samples, such as blood and urine, contain low-molecular-weight metabolites, such as amino acids and sugars, that are produced and transformed during metabolic processes within the body. Analyzing types and quantities of these metabolites is believed to provide valuable insights into an individual’s health status and pathological condition as they fluctuate in response to factors such as genetic background, lifestyle, disease, and medications.

Metabolomics is the field of research that comprehensively measures low-molecular-weight metabolites in order to understand the state of the body at the molecular level. In recent years, metabolomics has been expected to analyze the diverse human samples accumulated in domestic and international biobanks and integrate them as big data. Identifying metabolites that fluctuate due to specific diseases or pathological conditions from this big data has the potential to lead to the discovery of biomarkers — indicators useful for diagnosis and the search for therapeutic targets. This may form the basis of precision medicine, whereby treatments are selected based on individual patient characteristics.

In collaboration with researchers at Kyushu University, the Institute of Science Tokyo, and Burker Japan Co., Ltd., Researchers at AIST have established a fast and highly reproducible analytical method. This method uses matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) combined with ion mobility (IM) separation technology to analyze low-molecular-weight metabolites in human plasma. They confirmed that this method can stratify patients across multiple cancer types.

Since low-molecular-weight metabolites such as amino acids and sugars, present in the blood fluctuate under the influence of lifestyle factors and diseases, analyzing these metabolites in a large number of biological samples with diverse genetic backgrounds and pathological conditions, is expected to reveal characteristics of health status and disease states. However, conventional methods of analyzing low-molecular-weight metabolites have faced challenges regarding measurement efficiency and reproducibility. This makes it difficult to have large-scale sample analysis (ranging from thousands to hundreds of thousands of specimens) under the same standards.

We have developed a method to analyze low-molecular-weight metabolites using MALDI-MS. This method combines an extremely simple pretreatment procedure, involving only dilution with acetonitrile, with ion mobility (IM) separation technology. The analysis in the proposed method is also extremely fast, taking less than one second per sample, and yields highly reproducible results based on two parameters: mass-to-charge ratio (m/z) and ion mobility. Furthermore, we confirmed that the information on multiple metabolites in blood obtained through this method can be used to distinguish and stratify healthy individuals from patients with various types of cancer, such as gastric and colorectal cancer.

Metabolomics, which systematically analyzes low-molecular-weight metabolites, is expected to generate big data from the diverse human samples accumulated in biobanks, thereby facilitating the discovery of metabolites that serve as disease markers (biomarkers) and laying the groundwork for precision medicine. The method developed in this study is a significant step toward accelerating these efforts.

Details of this research were published in the “Microchemical Journal” on March 9, 2026.

Journal: Microchemical Journal
Title: Ultrahigh-throughput metabolomics for large-scale studies using matrix-assisted laser desorption/ionization-ion mobility-mass spectrometry
Authors: Hiroaki Takeda, Daisuke Miura*, Teppei Shimamura, Yoshinori Fujimura, Masatomo Takahashi, Mitsuru Shindo, Ryo Nakabayashi, Takashi Nirasawa, and Takeshi Bamba*
DOI：10.1016/j.microc.2026.117523