Development of Mass Spectrometry Technology and Its Application in Biological Research

Mass spectrometry, a widely used technology in current biological research, is increasingly important due to its advantages in rapidly and efficiently determining complex biological macromolecules and small molecules. In this issue, we will discuss the development of mass spectrometry technology and its applications in biological research.

Principle of Mass Spectrometry
Mass spectrometry analysis technology is a method used to analyze and identify samples by measuring and analyzing the mass-to-charge ratio of sample ions. A mass spectrometer generally consists of three parts: an ion source, a mass analyzer, and a detector. The mass analyzer is the core component of a mass spectrometer, determining the sensitivity, resolution, ion fragment generation capability, and accuracy of the analysis. Before analysis, samples must be ionized to carry a certain charge. Next, the charged ions are driven by an accelerating electric field and enter an analysis electric or magnetic field. Due to differences in mass and charge of the sample ions, their trajectories in the analysis field differ. This allows the separation of different ions by analyzing their trajectories and enables qualitative and quantitative measurements of the sample's information, purity, and other characteristics.

History of Mass Spectrometry
The first mass spectrometer was invented by J. J. Thomson over 90 years ago, primarily used for determining inorganic elements in chemical experiments. As mass spectrometry technology expanded and computer technology developed, it gradually began to be used for analyzing more complex biological molecules, including amino acids, proteins, lipids, and carbohydrates. Although mass spectrometry has a shorter history and has been applied to biological research for a shorter time compared to instruments like microscopes, it is an irreplaceable method for precisely analyzing and identifying biological molecules in biological research.

Common Types of Mass Spectrometry
Biological research often involves complex macromolecules, including proteins, nucleic acids, carbohydrates, lipids, and various small molecules. The properties of various biological molecules differ greatly. Therefore, there are several types of mass spectrometers used in biological research. The commonly used ones include:

1. Quadrupole Mass Spectrometer

The mass analyzer of a quadrupole mass spectrometer is composed of four rod-shaped electrodes. By applying alternating frequency fields between paired electrodes, only ions of a certain mass are allowed to pass through the quadrupole to the detector, enabling rapid analysis of ions within this range. Its features include a simple instrument structure and fast scanning speed, but relatively low resolution.
2. Time-of-Flight Mass Spectrometer (TOF)

In this type of mass spectrometer, the mass-to-charge ratio of ions is determined by analyzing the flight time of ions in a vacuum flight tube. Through continuous improvements, TOF mass spectrometers have significantly enhanced resolution and accuracy. After a post-correction procedure, the accuracy can reach the parts per million (PPM) level, and the detectable ion mass range can reach several hundred thousand.
3. Ion Trap Mass Spectrometer

An ion trap mass spectrometer is a type of tandem mass spectrometer where the ion trap is the core component, serving as both the collision chamber and the mass analyzer. Before analysis, ions are accumulated and stored, making the ion trap mass spectrometer advantageous in ion storage and selection.
4. Ion Cyclotron Resonance (ICR) Mass Spectrometer

The ion cyclotron resonance mass spectrometer is designed based on the cyclotron motion of ions in a magnetic field. Among these types of mass spectrometers, ion cyclotron resonance mass spectrometers have relatively high resolution and accuracy, with the Orbitrap being a typical representative of high-precision mass spectrometers.

Applications of Mass Spectrometry in Biological Research

1. Detection of Biological Metabolites

Mass spectrometry technology has a long history of development in the detection of small molecules, with mature methods for their determination and analysis. Currently, mass spectrometry can accurately determine various biological small molecules, including amino acids, fatty acids, organic acids and their derivatives, monosaccharides, prostaglandins, thyroid hormones, bile acids, cholesterol and steroids, biogenic amines, lipids, carbohydrates, vitamins, trace elements, etc.
2. Detection of Biological Macromolecules

Proteins, carbohydrates, nucleic acids, and lipids are the main components that constitute organisms and the executors of biological activities. Most biological research ultimately revolves around these biological macromolecules. Although mass spectrometry analysis of macromolecules is more complex than that of small molecules, the rapid development of mass spectrometry technology has made the analysis of these biological macromolecules accurate and fast.
3. Drug Analysis and Detection

The composition of drugs varies widely. For example, modification at a critical site of antibody drugs can greatly affect their efficacy, making traditional drug analysis techniques very challenging for biological drugs. Thanks to the efficiency and accuracy of mass spectrometry, it is often used for amino acid sequence analysis of peptide and protein drugs (including glycoproteins). Additionally, mass spectrometry can be used for the analysis of natural drugs, drug metabolism research, and the analysis of traditional Chinese medicine components.
4. Identification of Microorganisms

There is a vast diversity of microbial species, and differences in genetic sequences among different microbes lead to variations in bacterial protein sequences. Mass spectrometry determines the peptide fingerprint profiles of microorganisms and compares them with database information to identify the microorganisms. Additionally, mass spectrometry can analyze specific carbohydrates or esters produced by certain microorganisms, further aiding in the identification of target microorganisms.