What Are the Different Uses of an Ionization Mass Spectrometer?

Mass spectrometry (also known as mass spectrometry) is a spectroscopic method that is juxtaposed with the spectrum. Generally, it refers to a specialized technique widely used in various fields to identify compounds by preparing, separating, and detecting gas-phase ions. Mass spectrometry can provide a wealth of structural information in one analysis. Combining separation technology with mass spectrometry is a breakthrough in the scientific method of separation. Among many analytical methods, mass spectrometry is considered to be a universal method that has both high specificity and sensitivity and is widely used. Mass spectrometers generally consist of a sample introduction system, an ion source, a mass analyzer, a detector, and a data processing system.

Chinese name: Mass spectrometry
Foreign name: mass spectrum

nickname: Mass spectrometry
Classification: Spectral method alongside spectrum
Features: Provides richer structural information

Mass spectrum definition

Mass spectrometry is an analytical method for measuring the mass-to-charge ratio (mass-to-charge ratio) of ions.

Joseph John Thomson It is to ionize each component in the sample in the ion source, generate charged ions with different charge-to-mass ratios, and form an ion beam through the action of an accelerated electric field to enter the mass analyzer. In the mass analyzer, the electric and magnetic fields are used to disperse the opposite velocity, and they are respectively focused to obtain a mass spectrum to determine the mass. The first mass spectrometer was made in 1919 by British scientist Francis Aston. Aston used this device to discover multiple element isotopes, studied 53 non-radioactive elements, and found 212 of the 287 nuclides that occur naturally. He won the Nobel Prize for Chemistry in 1922 for this.

Mass Species

There are many types of mass spectrometers, and their working principles and applications are also very different. From an application perspective, mass spectrometers can be divided into the following categories:

Organic mass spectrometer: It is divided into:

Gas chromatography-mass spectrometer (GC-MS)

Among these instruments, due to the different working principles of mass spectrometers, there are gas chromatography-quadrupole mass spectrometer, gas chromatography-time of flight mass spectrometer, gas chromatography-ion trap mass spectrometer, and so on.

Liquid chromatography-mass spectrometer (LC-MS)

Similarly, there are liquid chromatography-quadrupole mass spectrometer, liquid chromatography-ion trap mass spectrometer, liquid chromatography-time of flight mass spectrometer, and various liquid chromatography-mass spectrometry-mass spectrometers.

Other organic mass spectrometers include:

Matrix-assisted laser desorption time of flight mass spectrometer (MALDI-TOFMS), Fourier transform mass spectrometer (FT-MS)

Inorganic mass spectrometers, including:

Spark source dual focus mass spectrometer.

Inductively coupled plasma mass spectrometer (ICP-MS).

Secondary ion mass spectrometer (SIMS)

But the above classification is not very rigorous. Because some instruments have different accessories and have different functions. For example, if a gas chromatography-double focusing mass spectrometer is switched to a fast atom bombardment ionization source, it will no longer be a gas chromatography-mass spectrometer, but will be called a fast atom bombardment mass spectrometer (FAB MS). In addition, some mass spectrometers can be connected to both gas chromatography and liquid chromatography, so it is not easy to fall into a certain category. Among the above types of mass spectrometers, the largest and most widely used are organic mass spectrometers.

In addition to the above classifications, the mass spectrometers can be divided into dual-focus mass spectrometers, quadrupole mass spectrometers, time-of-flight mass spectrometers, ion trap mass spectrometers, Fourier transform mass spectrometers, etc. from the different mass analyzers used by mass spectrometers.

MS applications

Mass spectrometry is an identification technique that plays a very important role in the identification of organic molecules. It can quickly and extremely accurately determine the molecular weight of biological macromolecules, making proteomics research from protein identification to advanced structural studies and interactions between various proteins.

With the development of mass spectrometry technology, the application fields of mass spectrometry technology are becoming wider and wider. Mass spectrometry has the advantages of high sensitivity, small sample usage, fast analysis speed, and simultaneous separation and identification. Therefore, mass spectrometry is widely used in chemistry, chemical engineering, environment, energy, medicine, sports medicine, criminal science and technology, life Science, materials science and other fields.

There are many types of mass spectrometers, and the application characteristics of different instruments are also different. Generally speaking, samples that can be vaporized at about 300C can be preferentially analyzed by GC-MS. Because GC-MS uses EI sources, the mass spectrum information obtained can be analyzed Library inspection

Mass spectrometer Cable. Capillary columns also perform well. If you can't vaporize around 300C, you need to use LC-MS analysis. At this time, the molecular weight information is mainly obtained. If it is tandem mass spectrometry, some structural information can also be obtained. If it is a biological macromolecule, LC-MS and MALDI-TOF analysis are mainly used to obtain molecular weight information. For protein samples, the amino acid sequence can also be determined. The resolution of a mass spectrometer is an important technical indicator. A high-resolution mass spectrometer can provide the compound composition formula, which is very important for structure determination. Dual-focus mass spectrometers, Fourier transform mass spectrometers, and time-of-flight mass spectrometers with reflectors all have high-resolution capabilities.

Mass spectrometry has certain requirements for samples. The samples analyzed by GC-MS should be organic solutions. Organic substances in aqueous solutions cannot generally be determined. They must be extracted and separated into organic solutions, or headspace sampling techniques should be used. Some compounds are too polar and easily decompose during heating, such as organic acid compounds. At this time, esterification treatment can be performed, and the acid is converted to an ester, followed by GC-MS analysis. From the analysis results, the structure of the acid can be inferred. If the sample cannot be vaporized or esterified, it can only be analyzed by LC-MS. The LC-MS sample is preferably an aqueous or methanol solution. The LC mobile phase should not contain non-volatile salts. For polar samples, the ESI source is generally used, and for non-polar samples, the APCI source is used.

History of Mass Spectrometry

As early as the end of the 19th century, E. Goldstein observed positively charged particles in low-voltage discharge experiments, and then W. Wein discovered that positively charged particle beams were deflected in a magnetic field. These observations provided preparation for the birth of mass spectrometry.

The first mass spectrometer was made in 1919 by British scientist Francis William Aston. Aston used this device to discover a variety of isotopes, studied 53 non-radioactive elements, found 212 of the 287 nuclides that occur naturally, and proved atomic mass loss for the first time. For this he won the Nobel Prize in Chemistry in 1922.

By the 1920s, mass spectrometry gradually became an analytical method and was used by chemists. Since the 1940s, mass spectrometry has been widely used for organic substance analysis.

Mass spectrometry principle By the Chemical Ionization (CI) source, mass spectrometry could detect thermally unstable biomolecules for the first time; around the 1980s, with fast atom bombardment (FAB), electrospray (ESI), and matrix-assisted laser analysis (MALDI) With the advent of new "soft ionization" technologies, mass spectrometry can be used to analyze samples of high polarity, difficult to volatilize, and thermally unstable, and the rapid development of biological mass spectrometry has become one of the hot spots in modern science. Because of its advantages such as rapidness, sensitivity, and accuracy, and the ability to perform protein sequence analysis and post-translational modification analysis, biological mass spectrometry has unquestionably become the most important means for proteomics to analyze and identify peptides and proteins. Mass spectrometry can provide a wealth of structural information in one analysis. Combining separation technology with mass spectrometry is a breakthrough in the scientific method of separation. For example, the use of mass spectrometry as a detector for gas chromatography (GC) has become a standardized GC technique and is widely used. Because GC-MS cannot separate unstable and non-volatile substances, a combination of liquid chromatography (LC) and mass spectrometry has been developed. LC-MS can simultaneously detect the position of glycopeptides and provide structural information. The combined technique of capillary electrophoresis (CE) and mass spectrometry was first reported in 1987. CE-MS can simultaneously obtain migration time, molecular weight, and fragmentation information in one analysis, so it is complementary to LC-MS.

Among many analytical methods, mass spectrometry is considered to be a universal method that has both high specificity and sensitivity and is widely used. The development of mass spectrometry is of great significance to many fields such as basic scientific research, national defense, aerospace, and other industries and civilians.

Mass spectrometry

Mass spectrometry with the advancement of science and technology, since the 1980s, four soft ionization technologies have been produced, namely plasma desorption (PD-MS), fast atom bombardment (FAB), electrospray (ESI), and matrix-assisted laser desorption. / Ionization (MALDI).

The principle of plasma desorption is: nuclear fission fragments using radioisotopes are used as primary particles to bombard a sample and ionize it. The sample is dissolved in a suitable solvent and coated on 0.5-1 & micro; m thick aluminum or nickel foil. The nuclear fission fragments are from the back A large amount of energy is passed through the metal foil to the sample molecules, causing them to desorb and ionize. In the preparation of samples, the use of nitrocellulose as a substrate allows PD-MS to be used to analyze peptide and protein samples with molecular weights up to 14 000.

The principle of fast atom bombardment is that a beam of high-energy particles, such as argon and xenon atoms, is shot at the sample molecules in the liquid matrix to obtain sample ions. In this way, excimer ion peaks that provide molecular weight information and compound structure information can be obtained. Debris peak. Fast atom bombardment is easy to operate, has high sensitivity, and can obtain stable ion current for a long time. When used in the analysis of oligosaccharides and their derivatives in most organisms, the molecular weight can reach 6000. And in this mass range, its sensitivity is much higher than in the 15000 range.

Mass spectrometer The sensitivity of the new generation of full-acceleration instruments. In addition, Camim et al. Used FAB-MS to analyze the four oligosaccharide components obtained from Hafnia alvei, detected oligosaccharides that could not be observed by NMR, and revealed the heterogeneity of the oligosaccharide structure.

The principle of electrospray ionization is: an electric field is applied to the top of the sprayer to provide a net charge to the droplets; under a high electric field, the surface of the droplet generates a high electrical stress, which causes the surface to be damaged to produce a droplet; the solvent in the charged droplet is evaporated; Ions on the droplet surface "evaporate" into the gas phase and enter the mass spectrometer. In order to reduce the surface energy of the droplets, heating to 200-250 ° C can improve the spraying efficiency. FAB-MS can show fragment ions, but can only generate single-charged ions, so it is not suitable for analyzing molecules whose molecular weight exceeds the mass range of the analyzer. ESI can generate multi-charged ions, each with an accurate small m / z value. In addition, product ions of multi-charged parent ions can be generated, which can produce more structural information than product ions of single-charged ions. Moreover, ESI-MS can complement or enhance the information obtained by the FAB, even for small molecules.

Mass spectrometer

Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) is a mass spectrometry technique that was introduced in the late 1980s and developed rapidly. The ions generated by this ionization method are usually detected by a time of flight (TOF) detector. Therefore, MALDI and TOF are often referred to as matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). MALDI-TOF-MS technology has revolutionized the traditional mass spectrometry technology, which is mainly used for the research of small molecular substances, and has entered a new era of the development of biomass mass spectrometry technology. The characteristic of this technology is that it is called "soft ionization", which generally produces stable molecular ions, so it is an effective method for determining the molecular weight of biological macromolecules. It is widely used in biochemistry, especially for the analysis of proteins and nucleic acids. Breakthrough progress. The application of MALDI-MS in sugar research also shows some potential and application prospects. In addition, it also shows unique potential and application prospects in polymer chemistry, organic chemistry, metal organic chemistry, pharmacy and other fields. It has become an ideal tool for the majority of scientific and technological workers to study the molecular weight, purity and structure of macromolecules. It is widely used in the field of biochemistry,

Mass Specimen Import

An important feature of the mass spectrometry method is that it has very high sensitivity to samples in various physical states, and it is independent of the molecular weight of the analyte to a certain extent. However, because the mass analyzer of the mass spectrometer is installed in the vacuum chamber, the analysis sample can only be introduced into the ion source through specific methods and pathways, ionized, and then introduced into the mass analyzer for analysis.

Nitrogen Mass Spectrometer Leak Detector quality analysis. All components used to complete such sample introduction tasks are generally referred to as sample introduction systems. The sample introduction method can be divided into direct introduction method and indirect introduction method. The indirect introduction method can be further subdivided into chromatographic introduction and membrane injection. The direct introduction method is to place a low-volatile sample directly on the probe, send the probe into a vacuum chamber, and then heat the probe by applying a large current, so that the temperature of the probe rises to several hundred degrees (generally not exceeding 400 ). ), The sample molecules are volatilized to form a vapor when heated, and the vapor is directly introduced into the ion source for ionization under the effect of the vacuum gradient in the vacuum chamber. Because temperature has a large effect on the volatility of the sample, it is necessary to precisely control the temperature, but this also makes selective sampling of solids possible. This method is mainly suitable for samples with low volatility and good thermal stability. For hardly volatile and thermally unstable samples, the desorption ionization (DI) method is mainly used.

Chromatography is the most commonly used method for indirect sample introduction in mass spectrometry. One of the research hotspots of this sampling system is the interface technology between mass spectrometry and chromatography. GC samples can be directly introduced into the ion source of the mass spectrometer through the capillary. If the GC's carrier gas flow rate is large, you can add a stage vacuum in front of the ion source or use a jet separator to split the carrier gas (such as small molecule gases such as He) and enrich the analyte. LC-MS often uses electrospray technology to extract samples from the chromatographic effluent while introducing samples. The advantage of this method is that it does not require complicated maintenance and debugging of the instrument, and has high sensitivity and extremely fast response speed. . In addition to the classic GC and LC used for mass spectrometry sample introduction, supercritical fluid chromatography (SFC) and capillary electrophoresis (CE) can also be combined with mass spectrometry technology, greatly expanding the flexibility of sample introduction. If DI technology is used, thin-layer chromatography, paper chromatography, etc. can be used in mass spectrometry analysis, which can greatly reduce costs if efficiency is allowed.

With the popularization of mass spectrometry in environmental analysis, membrane sampling technology has gradually gained importance. In common membrane sampling systems, most of the semi-permeable membranes are made of silicon polymers. Such semi-permeable membranes allow certain small molecules of organic compounds to enter the vacuum system through the membrane wall, while a large amount of matrix and solvents in the sample are impermeable. Therefore, the membrane sampling technology (MI) is particularly suitable for continuous online monitoring of low-level analytes, such as MI-MS, and is expected to have good applications in environmental monitoring and industrial control.

Furnace or cell injection is often used in the calibration of mass spectrometers and the identification of organic structures. Most commercial instruments are equipped with this type of injection system. This system can provide stable sample concentration for a long time, which is convenient for calibration of the instrument and slow scanning of the object to be measured, so as to obtain accurate signals. Of course, this method requires the sample to have lower volatility and better thermal stability. In addition, the method consumes a large amount of sample.

Mass ion source

In the early mass spectrometry studies, the samples involved were generally inorganic.The detection purposes included the determination of atomic weight,

On-line mass spectrometry system Isotopic abundance, determination of elemental composition, etc. In response to these requirements, the ion sources that need to be used mainly include inductively coupled plasma (ICP), microwave plasma torch (MPT) and other microwave induced plasmas (MIP), arcs, sparks, glow discharges, etc., which can be almost used for atoms Emission spectrum excitation sources are available. The detection objects of mass spectrometry are mainly organic and living active substances. Some special ionization sources (relative to AES excitation sources) are needed. These ionization sources can be divided into 4 categories, namely electron impact ionization (EI), chemical ionization (CI), desorption ionization (DI), and spray ionization (SI), as shown in the following table. In addition to EI, each ionization source can obtain a large number of positive and negative ions at the same time, and the type of molecular ions is related to the medium or matrix in the ionization process. For example, CI can generate (MH), (M NH4), (M Ag), (M Cl) -plasma as molecular ions, and it can also generate similar fragment ions.

Common MS Ionization Source Tables for Organic Matter Analysis

Ionization source	Ionizing reagent	Suitable sample
Electron ionization (EI)	electronic	Gaseous sample
Chemical Ionization (CI)	Gas ion	Gaseous sample
Desorption Ionization (DI)	Photon	Solid sample
Spray ionization (SI)	High energy electric field	Hot solution

Different ions generated by the ionization source can react with each other, making the ionization results more abundant and complicated. For example, under the action of EI, a large number of ions can be generated, and ions with larger internal energy can spontaneously crack to produce more fragment ions when they collide with neutral molecules (such as He). This type of ion-molecule reaction is generally difficult to complete, and often retains some parent ions while obtaining many fragment ions. However, by increasing the internal energy of the ion (such as adjusting the collision time, EI energy, and the number of neutral particles, etc. Can cause this

Mass spectrum The ion-molecule reaction proceeds completely; conversely, if the internal energy of the ion is reduced, it is possible to obtain a stable ion instead of a fragment of the ion. Relative to EI, CI, DI and SI are all soft ionization sources. With the help of laser and matrix, DI can even instantaneously ionize solid compounds that are difficult to volatilize and thermally unstable deposited on a certain surface to obtain relatively complete molecular ions. The emergence of SI solves the problem of biological macromolecular injection, and provides a very convenient and effective method for the application of mass spectrometry in the field of life sciences, especially the determination of macromolecular life-active substances such as proteins and DNA. Its role is also due to its role The founder received the Nobel Prize in Chemistry in 2002 and has received worldwide attention. To examine the performance of the ionization source, the parameters generally required are signal strength, background signal strength, ionization efficiency, and internal energy control capabilities.

Mass spectrometer

Gaseous ions can be separated in space or time according to the mass-to-charge ratio by appropriate electric or magnetic fields. Broadly speaking, a device capable of separating and resolving gaseous ions is a mass analyzer. A variety of mass analyzers have also been used or studied in mass spectrometers. Only the mass analyzers widely used in commercial instruments are introduced here, that is, fan-shaped magnetic fields, time-of-flight mass analyzers, quadrupole mass analyzers, Quadrupole ion trap and ion cyclotron resonance mass analyzer.

1 sector magnetic field

The fan-shaped magnetic field is the earliest mass analyzer in history. In addition to its significance in the history of mass spectrometry, it also has many advantages, such as good reproducibility, resolution independent of mass size, and the ability to scan faster (per second 10 mass-to-charge ratio units). However, in the present miniaturized mass analyzer, the proportion of the fan-shaped magnetic field is not large, because if the volume and weight of the magnetic field are reduced, the strength of the magnetic field will be greatly affected, thereby greatly weakening its analysis performance. However, with the continuous emergence of new materials and technologies, this situation is expected to change in the future.

2 Time-of-Flight Mass Analyzer

Compared with other mass analyzers, the time-of-flight mass analyzer (ie TOF) has the advantages of simple structure, high sensitivity, and wide mass range (because the slow speed of large molecular ions makes it easier to measure), especially when combined with MALDI technology Even more so. In the past, mass spectrometry analysis of molecules with a mass-to-charge ratio of more than 10 to the fourth power was achieved using TOF. At present, the mass-to-charge ratio that this mass analyzer can measure is close to 10 to the sixth power. However, compared to other mass analyzers (such as ICR), the resolution and dynamic linear range of TOF are not ideal. For example, for organic compounds with molecular weights greater than 5000, the isotopic peaks are not well resolved. However, the accuracy of mass measurement of macromolecules can reach 0.01%, which is much better than that of traditional biochemical methods (such as centrifugation, electrophoresis, size chromatography, etc.).

In TOF, ions with different mass-to-charge ratios must enter the drift tube with the same initial kinetic energy at the same time, so as to ensure that the drift time is inversely proportional to the square root of the mass. In order to ensure that ions of different mass-to-charge ratios enter the drift tube with the same initial kinetic energy at the same time point, a pulsed ion source (such as a MALDI ion source using pulsed laser radiation) is often used.

Mass spectrometry However, in order to reduce this difference, the ions are often cooled. The cooling time is generally tens of milliseconds. The cooled ions are reintroduced into the electric field to accelerate. Can basically eliminate the difference in speed. However, in accurate measurement, after the ions are accelerated, their temporal and spatial distribution needs to be corrected, which is commonly referred to as time focusing and space focusing. This correction increases the accuracy of the TOF measurement, but also increases the complexity of the instrument.

3 Quadrupole Mass Analyzer

The structure of a quadrupole mass analyzer is to place four metal cylinders in parallel on two planes that are perpendicular to each other. If the horizontal direction is defined as the x direction, the vertical direction is the y direction, and the direction parallel to the metal cylinder is the z direction, a high-frequency voltage of ± (UV cost) is applied to the x and y electrodes (V is the voltage amplitude) , U is the DC component, is the circular frequency, and t is the time), then an alternating electric field shaped like a saddle is formed in the space between the four metal cylinders. The quadrupole mass analyzer can perform mass scanning or mass selection by adjusting the electric field. The size of the mass analyzer can be small and the scanning speed is fast. It is relatively simple to operate or mechanically construct. However, the resolution of this instrument is not high; the rod body is easily contaminated; and maintenance and adjustment are difficult.

4 Ion Trap

The ion trap and the quadrupole mass analyzer have many similarities. If the two ends of the quadrupole mass analyzer are added with an appropriate electric field to seal them, the ions in the quadrupole will be affected by x, y, and z. The combined action of electric field forces in three directions allows ions to stay in the stable region for a longer time under the combined action of these three forces, just like an electric field potential well, so such a device is called an ion trap. Therefore, it is often thought that the difference between a quadrupole mass analyzer and an ion trap is that the former is two-dimensional and the latter is three-dimensional.

The ions inside the ion trap are always doing complex movements. In this complex movement, the characteristic information related to mass is included. Based on this characteristic information, many new modes of ion trap operation have been developed, greatly expanding the mass range of the ion trap mass analyzer and improving mass resolution.

Although the movement of ions in the ion trap is complex, as far as the ion trap mass analyzer itself is concerned, it has many unique advantages. It is mainly capable of conveniently performing cascade mass spectrometry measurements and can withstand higher pressures (such as 0.1 Pa). In addition, this type of mass analyzer is relatively inexpensive and small in size, and is widely used as a chromatographic detector. Among the miniaturization of mass spectrometers, the miniaturization of ion traps has achieved remarkable results. The work of Professor Cooks of Purdue University is particularly prominent. The cylindrical ion trap and rectangular ion trap developed have not only overcome the disadvantages of ion traps that are difficult to process, but also further reduced costs, simplified operations, and significantly reduced The weight reduces the volume and can even be made into a mass sensor, which is expected to play a role in field environmental monitoring, national defense, criminal investigation, security inspection, industrial process control and other fields.

5 Ion cyclotron resonance mass analyzer

To some extent, the ion cyclotron resonance (ICR) mass analyzer is somewhat similar to NMR. ICR has a very high mass resolution, can detect large mass ions, perform non-destructive analysis of ions and multiple measurements, has high sensitivity and the ability to cascade mass spectrometry, is an important application in the field of modern mass spectrometry Quality Analyzer.

In order to further improve the mass resolution of the mass analyzer, a common measure is to combine a fan-shaped magnetic field with an electric field to form a dual-focus mass analyzer, while the resolution of the FT-ICR can be as high as 10 to the power of six.

Mass Detector

There are many types of detectors for mass spectrometers. Here we only briefly review the more common detectors, such as electron multipliers and their arrays, ion counters, inductive charge detectors, and Faraday collectors.

Electron multipliers are one of the more widely used detectors in mass spectrometers. A single electron multiplier tube basically has no spatial resolution and is difficult to meet the growing needs of mass spectrometry. Therefore, people have miniaturized the electron multiplier and integrated it into a miniature multi-channel plate (MCP) detector, which has played an important role in many practical applications. In addition to this type of array detector, detectors widely used in spectroscopy, such as charge-coupled devices (CCDs), have also been increasingly used in mass spectrometers. The IPD (ion-to-photon) detector has attracted much attention because it can work stably for a long time under high pressure.

Ion counter is a very sensitive detector, which is usually used for calibration of ion source or characterization of ionization efficiency. For general electron multiplier tubes, an ion can trigger 5 to 8 electrons of 10 within the negative 7th power of 10 seconds. For most mass spectrometers working in the fields of organic matter detection and biochemical research, Its sensitivity is sufficient. However, in some geochemical and cosmological studies, an ion counter is required for detection. The detection current can be lower than the level of one ion per second. Generally, the signal of the ion source is also at least 10 of the detection limit of the ion counter. 10 times power.

Inductive charge detectors are also called imaging current detectors, often associated with ICR

Mass spectrum Combined with mass analyzer. Because it measures inductive charge (current), its sensitivity is low due to its low induction efficiency. However, when it is used in combination with ICR, etc., ICR still has very high sensitivity because it allows non-destructive measurement and repeated measurement of ions. A Faraday plate (cup) is the simplest detector. This detector connects a metal piece with a specific structure to a specific circuit, collects electrons or ions falling on the metal piece, and then performs amplification and other processing to obtain a mass spectrum signal. In general, this type of detector has no gain and its sensitivity is very low, limiting its use. However, in some cases, this ancient detector plays an irreplaceable role. Array detectors, such as those produced by the University of Indiana (Hieftje), make use of the above characteristics of Faraday Cup detectors.

Progress in Mass Spectrometry

1 Desorption Electrospray Ionization

In 2004, Cooks et al. Reported a new mass spectrometry method for non-destructive detection of solid surfaces based on electrospray desorption ionization (DESI).

The charged droplets and ions generated by electrospray directly hit the surface of the analyte, and the analyte to be adsorbed on the surface

LC-MS The impact of charged ions desorbs from the surface and is ionized, and then enters the mass analyzer through the sampling cone of the mass spectrometer. The obtained mass spectrum is very similar to the conventional electrospray mass spectrum, and single or multiple charged molecular ions can be obtained. Electrospray desorption ionization technology can be regarded as a combination of electrospray technology and desorption technology, and is similar to secondary ion mass spectrometry. The difference is that both the desorption ionization technique and the secondary ion mass spectrometry technique are completed under vacuum conditions, while the electrospray desorption ionization process is completed under atmospheric pressure. Because this method does not require sample pretreatment, it can ionize explosives, pigments, proteins, etc. adsorbed on the solid surface at atmospheric pressure, and even directly detect the analytes on the surface of thin-layer chromatography, thus achieving mass spectrometry. Fast and sensitive determination. DESI is an emerging ion source. Its biggest advantage is that it can ionize substance molecules at atmospheric pressure, thereby achieving sensitive, fast, and highly selective online monitoring of the substance to be measured. The electrospray desorption ionization method is widely used and can be used for the determination of polar compounds, non-polar compounds, high molecular weight compounds, and low molecular weight compounds. DESI-MS can be used for the analysis of natural products of plant tissues, without the need for sample pretreatment processes such as extraction; in addition, this technology has also been used in the fields of proteomics, metabolomics and diagnostics, drug detection and other fields, and has achieved good the result of. It is worth mentioning that the Cooks group combined DESI with a portable mass spectrometer and realized the analysis of drugs, plant tissues, explosives, biochemical warfare agent simulants, and agricultural chemicals.

2 Corona Direct Analysis in Real Time (CDART)

In 2003, American scientists invented the Corona Direct Analysis in Real Time (CDART) ionization technology and successfully combined it with a time-of-flight mass spectrometer with an atmospheric pressure interface to form a new mass spectrometer. This kind of mass spectrometer can directly perform real-time analysis under atmospheric pressure without any treatment on the surface of various gas, liquid and solid samples. The results can be obtained in a few seconds, which can make the mass spectrometry technology meet the needs of the scientific and technological fields. There is an urgent need and it is considered by academics as the "next quantum leap" and "revolutionary ion source" in the development of mass spectrometry technology.

Mass spectrometer

Combining it with an ion mobility spectrometer (IMS) is expected to develop a portable and dedicated instrument that can be used for field testing. Directly analyze the ionization source in real time. Normally corona discharge is used to make helium form metastable helium atoms, or make nitrogen form vibrationally excited nitrogen molecules (activated nitrogen). These high-energy components can be contacted with sample molecules. The latter is ionized by inelastic collision, and it is introduced into the mass analyzer for further analysis, and the required mass spectrum information of the analyzed sample can be obtained. CDART technology was originally developed (June 2003) by JEOL Corporation in the United States and used in the company's AccuTOF mass spectrometer with atmospheric pressure interface. In the same year (2003), the US Army's Edgewood Chemical Biological Weapon Center in Maryland began evaluating its capabilities as a chemical weapons detector. Research from both (JEOL Corporation and Edgewood Center) quickly demonstrated that this new technology can be used to identify hundreds of chemical substances, including chemical biological weapon preparations and their related compounds including their precursors, additives, reactions and degradation Products and detoxification by-products), pharmaceuticals, metabolites, amino acids, peptides, oligosaccharides, synthetic organic compounds and metal organic compounds, drugs, explosives and toxic industrial chemicals. Sample types include porous concrete, asphalt, human skin, coins, flight boarding cards, business cards, fruits, vegetables, condiments, beverages, biological fluids, trees and leaves, wine glasses, common laboratory equipment and clothing. Recent research has also been extended to the determination of proteins, the identification of polymers, the rapid analysis of antioxidants in rubber, the rapid analysis of fats in edible oils, the rapid analysis of binders, cement, and resins, and the detection of explosives in mud. Determination of lycopene on tomato surface, detection of opium in a single poppy seed, determination of capsaicin distribution in pepper, detection of unstable compounds released from onion slices, rapid detection of trace compounds in herbicides, orange peel

Mass spectrometer Detection of bactericides and more.

3 Extractive Electrospray Ionization

Based on the research of DESI-MS, Chen Huanwen et al. Creatively proposed the electrospray extraction ionization (EESI) technology. EESI technology was first used for the determination of liquid samples. The charged droplets and ions generated by electrospray collided with the sample droplets generated by atomization. The analyte in the sample solution was extracted and ionized, and the analyte ions were passed through the capillary interface. Introduce mass spectrometer.

Subsequently, Chen Huanwen and others successfully carried out metabolomics research based on the EESI-TOF-MS method and living breathing gas as samples. The research results were selected by Angew. Chem. Magazine as a VIP hot article and in the form of a cover picture Speed up publication. The experiment was performed on a commercial ESI ion source. The gas sample was introduced from the sheath gas inlet and collided with the charged droplets and ions generated by electrospray. After the molecules of the analyte were extracted and ionized, they were introduced into the mass spectrometer through a capillary. Due to its ingenious design and excellent performance, EESI-MS not only has the high sensitivity and specificity unique to mass spectrometry, but also can withstand a variety of samples, and does not require sample collection and separation. It can be used for living body biological samples. , Real-time, online analysis. Therefore, it is possible to solve the problem of rapid mass spectrometry analysis of clinical samples. From the published results, EESI-MS can detect not only polar and non-polar molecules contained in breathing gas, but also volatile and non-volatile molecules. Through the in-situ mass spectrometry analysis of the breathing gas, the fingerprints of all these molecules in the sample can be obtained within 1 second, and the structure identification of any component of interest can be ensured, ensuring the reliability of the measurement results. Their research results show that the human body will be able to detect an unusually large amount of urea in exhaled breath under extreme hunger or pathological conditions, which is consistent with the results of using proteins and fats to replace sugar for energy in the body, and it also gives many diseases The diagnosis provides a basis; glucose can be detected in the exhaled breath after taking dessert, which provides a new way for the diagnosis and research of diabetes, etc .; the data also clearly shows the different reactions of healthy Asians and Europeans to beer ; And showed the rapid determination of certain types of compounds through selective molecular-ion reactions, such as detection of the cause of bad breath patients. In fact, EESI-M can be seen as a medical diagnosis at the molecular level. According to the evaluation of scientists, the results of this study clearly show that if mass spectrometry is used for in vivo metabolomics research, it provides unprecedented effective tools for the diagnosis and treatment of various diseases in humans and the study of molecular cytological mechanisms of life activities. . Professor John B. Fenn, the Nobel Prize winner in chemistry in 2002 and the inventor of ESI technology, believes that this technology (EESI) will be widely used, and especially analytical chemists will be grateful. There is no doubt about this. Professor Cooks believes that EESI has opened up a new field of clinical diagnostic analytical chemistry and has epoch-making significance for the application of mass spectrometry in clinical medicine. After the research results were published, the CHIMIA journal of the Swiss Chemical Society decided to reprint them. Many academic journals in Europe and the United States, including British Chemical World, C & EN in the United States, German Technology Online, Medical News Today, Medilexicon, Hospitalsworldwide, Lab on a chip Other media have reported on this result in multiple languages, which is intended to quickly attract the attention of relevant industry personnel in various countries.

Mass spectrometry

1 Low temperature detector

The low temperature detector is also called a heat detector. When particles or ions hit the surface of a superconducting film, energy accumulates and generates heat, and neutrons, ions, electrons, and photons are sputtered from the surface. This process is not easy to find at room temperature. However, under low temperature conditions (<3K), the instantaneous "high temperature" caused by ion impact can be detected, thereby providing information on ion rate and energy. The low temperature detector has 100% efficiency, no quality discrimination, and theoretically no upper quality limit. Detection of large mass ions using electron multipliers and microchannel plates

MS applications During the measurement, the detection efficiency will be reduced due to the generation of secondary electrons, and the response signal of the low-temperature detector in the high-quality region will not decrease. This method that can detect the ion energy is helpful for the study of ionization mechanism. Commercially available array cryogenic detectors using superconducting tunnel junction detectors in 2002 detected m / z 400,000 macromolecules with a sensitivity of fmol. However, this detector needs to work in an extremely low temperature environment, which limits its application to a certain extent.

2 Microsphere plate detector

Tremsin and Naaman developed a microsphere plate detector (MSP) based on the principle of microchannel plate detection. Glass microspheres with a diameter of about 20 to 100 microns are treated with special materials and sintered to form a thin, porous glass plate. In this way, irregular channels can be formed between the two surfaces of the glass plate. The electrons are accelerated by the high voltage applied between the two surfaces, and when they pass through the curved channel, they hit another microsphere surface again to generate more electrons. After multiple cycles, the electron flow is detected on the other side of the glass plate. Compared with microchannel plates, microsphere plates have higher detection efficiency. When a microchannel plate is used, when the ions impinge on the surface between the channels, no electrons are generated; while when a microsphere plate is used, the surface receiving ions is a plurality of spherical surfaces, which greatly improves the detection efficiency. In addition, compared to microchannel plates, the cost of microsphere plates is much lower.

When Guilhaus et al. Used a microsphere plate detector with an orthogonal time-of-flight mass analyzer, the pulse width of a single ion was 800 ps (full width at half maximum).

3 other

Birkinshaw and Langstaff et al. Developed a focusing plate detection system consisting of a microchannel plate and an anode array. The anode array is a complementary metal oxide semiconductor device based on chip technology. It consists of an 18-micron-wide aluminum detection strip and corresponding circuits, which can be used to detect the pulse current generated by the microchannel plate. Compared with ordinary microchannel boards, the signal-to-noise ratio, sensitivity, and resolution have been improved, but the counting rate has not been improved.

Sinha and Wadsworth et al. Reported charge-coupled device (CCD) -based array detectors. The author replaced the photon-sensitive device in the charge-coupled device with a metal oxide semiconductor device, which can be directly used for the detection of ions. Detection of 5 ions.

Fuerstenau et al. Used active pixel sensing technology for ion detection and replaced the photodiodes in complementary metal oxide semiconductor devices with metal strips that could be used for charge collection. Unlike charge-coupled devices, each pixel in a complementary metal-oxide-semiconductor device has an independent amplification function in the circuit.

MS Outlook

In the 21st century, the development of modern science and technology poses new challenges to analytical testing technology. Unlike classic chemical analysis methods and traditional instrumental analysis methods, in modern analytical science, in situ, real-time, online, non-destructive, high-throughput, high sensitivity, high selectivity, and low loss have always been the goals pursued by analysts . Among many analytical methods, mass spectrometry is considered to be a method that has both high specificity and sensitivity and is widely used. The proposals of electrospray desorption ionization technology, real-time direct analysis of corona discharge ionization technology and electrospray extraction ionization technology meet the needs of the times and the requirements of scientific and technological development, and have opened a window for the rapid mass spectrometry analysis of complex samples.

Portable mass spectrometers are one of the hotspots of new mass spectrometers. The research on portable mass spectrometers mainly focuses on ionization technology and mass analysis technology. Detectors and commercialized detectors from SGE are mostly used as detectors. In order to adapt to the rapid development of ionization technology and mass analysis technology, it is urgent to develop high-performance ion detection technology, and low noise, high stability, wide mass range, low quality discrimination, long life, and low cost will be ion detection. Goals to be pursued in technological development.

Mass spectrometry, spectroscopy, and nuclear magnetic resonance methods are side by side, and for the time being there are few areas of intersection. In fact, the intersection between mass spectrometry and these classical spectroscopic methods is also a research area that deserves attention.

Biological mass spectrometry can provide fast, easy-to-solve multi-component analysis methods, and has the characteristics of high sensitivity, strong selectivity, and good accuracy. Its application range far exceeds the scope of radioimmunoassay and chemical detection. It is mainly used for the analysis of component sequences, structure analysis, molecular weight determination and content determination of various components in living organisms.
1. Application of nucleic acid detection: Molecular biology research of nucleic acids has become one of the most dynamic research directions in the fields of life chemistry, molecular biology and medicine. Through modern biological mass spectrometry technology, we can not only obtain the molecular mass of the oligonucleotide, but also obtain its sequence information through related technologies.
2.GCMS2004l224(FDA)T4
3()DNAl282%99%85%99%
4Hsu
5.()(TDM)(LCMS)LC MS

[1] Wu Li. Determination of micro-trace elements in biological samples, traditional Chinese medicine and water samples by inductively coupled plasma-mass spectrometry / emission spectrometry [D]. Sichuan University, 2007

[2] He Yihua. CCD-based small spectrum analysis instrument and new chemiluminescence technology [D]. Sichuan University, 2007

[3] Zhang Shengbang, Zhang Xuejun, Guo Yusheng. ICP-AES Determination of Calcium in Traditional Chinese Medicine [J] Spectroscopy and Spectral Analysis, 2004, (10).

[4] Zhuang Meihua, Zhu Huizhong, Cai Weixing, Ge Zhenxiang. Analysis of Trace Arsenic, Mercury, Lead in Gasoline by ICP-MS [J] Analysis and Testing Technology and Instruments, 2005, (04).

[5] Tao Guanhong, Fujikawa Yoko. Determination of total mercury in sediment by laser ablation-inductively coupled plasma mass spectrometry [J] Spectroscopy and Spectral Analysis, 2004, (09).

[6] Lang Chunyan, Wang Mohui, Zhu Xiaoxin. Catalytic Polarographic Determination of Trace Germanium in Lentinus edodes and Black Fungus by Microwave Digestion Samples [J] Analytical Laboratory, 2002, (03).

[7] Huang Zhiyong, Wu Xihong, Hu Guanglin, Zhuang Xiaxia, Wang Xiaoru. Research progress of elemental speciation analysis using high performance liquid chromatography / inductively coupled plasma mass spectrometry [J] Analytical Chemistry, 2002, (11).

[8] He Man, Lin Shoulin, Hu Shenghong. Combination of hydride generation injection and ICP-MS detection method [J] Spectroscopy and Spectral Analysis, 2002, (03).

[9] Liang Pei, Chen Hao, Hu Bin, Li Bin, Sun Dahai, Wang Xiaoru. Study on Determination of Trace Rare Earth Elements in Chinese Herbal Medicine by Inductively Coupled Plasma Mass Spectrometry [J] Journal of Analytical Science, 2002, (03).

[10] Liu Xiangsheng, Liu Gang, Gao Zhixiang, Pan Yuanhai, Zheng Yongzhang, Tong Jian. Study on Hydride Generation-Inductively Coupled Plasma Mass Spectrometry [J] Analytical Chemistry, 2003, (08).

[11] Jiang Ying, Xu Langlai, He Fuchu. Mass spectrometry analysis of phosphorylated proteome [J] Progress in Biochemistry and Biophysics, 2003, (03).

[12] Huang Zhenyu, Yu Yanling, Fang Caiyun, Yang Yiyuan. Research progress on identification of phosphorylated proteins by mass spectrometry [J] Journal of Chinese Mass Spectrometry Society, 2003, (04).

[13] He Jian, Yang Yuanyuan, Zhuang Yanxia, Wang Xiaoru, Yang Xiaodong, Song Haowei, Yu Wenjia, Wei Junfei, Zhou Zhen, AFDodonov. Development of a high-resolution electrospray ion source three-stage quadrupole-time of flight mass spectrometer [J] Journal of Instrumentation, 2003, (06).

[14] Qian Xiaohong. Proteomics and Biomass Mass Spectrometry [J] Journal of Mass Spectrometry, 1998, (04).

[15] Quetel, C.R, Vogl, J., Prohaska, T., Nelms, S., Taylor, PDP, De Bievre, P. Comparative performance study of ICP mass spectrometers by means of U isotopic measurements. Fresenius J. Anal. Chem, 2000, 3681 (2): 148-155.

[16] Guo, X.M, Sturgeon, RE, Mester, Z., Gardner, GJ UV light-mediated alkylation of inorganic selenium. Appl. Organomet. Chem. 2003, (17): 575-579.

[17] Jitaru, P, Infante, H. G, Adams, FC Multicapillary gas chromatography coupled to inductively coupled plasma-time-of-flight mass spectrometry for rapid mercury speciation analysis. Anal. Chim. Acta. 2003, 489: 45- 57.

[18] Guo, X.M, Sturgeon, RE, Mester, Z., Gardner, G J. UV vapor generation for determination of selenium by heated quartz tube atomic absorption spectrometry. Anal. Chem. 2003, 75: 2092-2099.

[19] Ryhage R. Anal. Chem. 1964, 36: 759-764