Mass Spectrometry’s History and Applications in Biological Research

As a commonly used technology in biological research today, mass spectrometry is known as one of the most popular techniques in biological research by quickly and efficiently measuring the advantages of complex biological macromolecules and small molecules.

The History of Mass Spectrometry

The first mass spectrometer, invented by J. J. Thomson, has been around for more than 90 years. It was mainly used for the determination of inorganic elements in chemical experiments. With the development of mass spectrometry technology and computer technology, mass spectrometer has gradually been applied in the analysis of more complex biomolecules, including amino acid, protein, lipids, sugar and so on. Although the history of mass spectrometry and the time it has been applied to biological research are much shorter than those of microscopes, the importance of mass spectrometry in biological research is irreplaceable as an accurate means of analyzing biomolecules.

Mechanism of Mass Spectrometry

Mass spectrometry is a method of analyzing a sample by measuring and analyzing the mass-to-charge ratio of the sample ions. The mass spectrometer is roughly divided into three parts, ion source, mass analyzer, and detector. The mass analyzer is the core component of the mass spectrometer, which determines the sensitivity, resolution, ability to generate ion fragments, and accuracy of the mass spectrometer. Before the sample is analyzed, it is first ionized in order to bring a certain charge to the sample molecule. Next, the charged ions will first driven through an accelerated electric field and fly into an analytical electric or magnetic field. Due to the difference in the mass of the sample itself and the ionization charge, the trajectories of the sample ions in the analysis electric field are also different, so that different ions can be distinguished by analyzing the trajectories of the ions. In addition, the qualitative and quantitative measurements of the information, purity and other characteristics of the sample can also be perform.

Types of Commonly Used Mass Spectrometers

The subjects of biological research are generally complex macromolecules, including proteins, nucleic acids, sugars, lipids, and various small molecules. The nature of various types of biomolecules also varies widely. Therefore, various types of mass spectrometers are used in biological research. The common used ones for biological research include quadrupole mass spectrometer, time of flight mass spectrometer, ion trap mass spectrometer and ion cyclotron resonance mass spectrometer.

Quadrupole Mass Spectrometer

The mass analyzer of the quadrupole mass spectrometer consists of four rod-shaped electrodes. An alternating field is applied between the two pairs of electrodes. The set frequency field allows only a certain mass of ions to pass through the quadrupole to the detector. A section of ions is rapidly analyzed. It is characterized by simple structure and fast scanning speed, but the resolution is relatively low.

Time of Flight Mass Spectrometer (TOF)

 The mass-to-charge ratio of ions determined by this type of mass spectrometer is derived by analyzing the time of flight of the ions in the vacuum flight tube. After continuous improvement, the TOF mass spectrometer has greatly improved in resolution and precision. The accuracy can reach PPM level after the post-correction procedure, and the detected ion mass range can reach several hundred thousand.

Ion Trap Mass Spectrometer

The ion trap mass spectrometer is a tandem mass spectrometer. The ion trap is the core of the mass spectrometer and is both a collision cell and a mass analyzer. Ion accumulation is stored prior to analysis, so the advantages of ion trap mass spectrometry lies in ion storage and selection.

Ion Cyclotron Resonance (ICR) Mass Spectrometer

ICR mass spectrometer is designed based on the characteristics of the ions moving in a magnetic field. ICR mass spectrometer is the instrument with high resolution and high accuracy in these types of mass spectrometers. Obitrap is a typical representative of high precision mass spectrometer.

Applications of Mass Spectrometry in Biological Research

Detection of Small Molecules in Biological Metabolism

Mass spectrometry has a long-term development in the detection of small molecules, and the measurement and analysis methods of small molecules are also quite mature. At present, mass spectrometry can accurately determine a variety of small biological molecules, including amino acids, fatty acids, organic acids and their derivatives, monosaccharides, prostaglandins, thyroxine, bile acids, cholesterol and steroids, biogenic amines, lipids, carbohydrates , vitamins, trace elements, etc.

Detection of Biological Macromolecules

Proteins, sugars, nucleic acids, and lipids are the main components of living organisms and the function of life activities. Most biological research is carried out around these types of biological macromolecules. Although mass spectrometry of macromolecules is more complex for smaller molecules, the analysis of these biomacromolecules becomes more accurate and faster with the rapid development of mass spectrometry.

Drug Analysis

The compositions of drugs vary widely. For example, the modification of a key site of antibody drugs may have a great impact on the efficacy of drugs. Therefore, it is difficult to analyze biopharmaceuticals with traditional techniques. Thanks to the high efficiency and accuracy of mass spectrometry, mass spectrometry is commonly used to analyze amino acid sequence of drugs such as glycoproteins such as biopeptides and proteins. In addition, mass spectrometry can also be used for natural medicine, drug metabolism research and Chinese medicine composition analysis.

Microbial Identification

There are many species of microorganisms, and the bacterial protein sequence is also different due to the differences in the genetic sequences of different species of microorganisms. Mass spectrometry is the very peptide fingerprint in the determination of a microorganism. Then,  compare it with the database information to identify the identity of the microorganism. In addition, mass spectrometry can also perform specific carbohydrates analysis or esters produced by certain microorganisms to identify target microorganisms. 

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