Sample inlet system of mass spectrometer

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Mass spectrometer of present day is well accommodated with numerous sample injection frameworks, the intent of which is to allow the introduction of wide ranges of individual samples into the ionization chambers by ensuring the minimum diminution of the high vacuum system.[1] In mass spectroscopy with high vacuum system, sample of different types such as solid, liquid or gases, depending on their vapor pressure injected through various inlet system.[2][3] The injected sample is then vaporized and followed by a complex ionization process directed towards the mass analyzer where individual mass depending on their charge deflected by a magnetic field.[4][5][6] The deflected masses are finally detected in detectors along with their abundance. Since last couple of decades, extensive research has been conducted on mass spectroscopy especially on generation of ion, ion source, mass filtration and detection. However, the research on sample injection or inlet source through which sample to be ionized is injected attracted fewer attention. In this article we will briefly, discuss about various sample inlet sources used in mass spectroscopy depending on the types of sample to be analyzed.[7]

Sample injection techniques of mass spectroscopy is highly dependent upon the type of sample and sample matrix which will be introduced into the ionization chamber. If the sample to be injected is highly volatile with high vapor pressure, it can be introduced directly into the ionization chamber and this process is called as direct vapor inlet method. This process is considered to be the most straightforward sample introduction method which inject the sample into the mass spectrometer through a needle valve. However, it is gas chromatography which is used as a pervasive method for the sample injection into the ionization chamber. In recent years the combination of GC-MS just revolutionized the application of mass spectroscopy. Most of the complex gaseous mixtures which are separated by gas chromatography, are injected into the mass spectrometer through a capillary connection. However, there are some complexity involved in choosing the connecting interfaces of GC-MS. Another widely used sample introduction technique for thermally labile compound is liquid chromatography. This technique is used for the samples such as liquid which cannot be injected by the gas chromatography. Moreover, there are two more inlet sources such as direct insertion probe and direct condensed vapor ionization, also available which are very useful while injecting specific samples depending on pressure and temperature sensitivity of the sample. In this article, we will try to explore extensively about the mentioned sample inlet sources, their mechanism, shortcomings, advantages and future applications.[8][9][10] Following table, representing some mass inlet techniques which will be discussed in this article.

Brief History[edit]

Mass spectroscopy, in its early days was used for the identification and quantification of the stable isotopes of various atoms in the periodic table.[11] In 1940, Consolidated Engineering Company Ltd. was the first commercial manufacturer who rolled out the mass spectrometer for industrial use. With time as its area of application expanded, mass spectrometer became a versatile analytical tool to analyze various compounds ranging from organic substances, gases, inorganic compounds, proteins, nucleotides and some other non-covalent complexes.[11][12] Using individual mass to charge ratio by applying the ion optics principle, mass spectroscopy helps the analytical chemist to understand the chemical properties of the individual molecules.[13] It is Wilhem Wien, a German physicist, who was studying streams of ionized gases in 1898, first introduced the concept of gas or liquid ionization by using high vacuum to characterize the individual chemical properties of the molecule.[12] After that, deflection of the ionized gaseous molecule and their change in trajectories by applying strong magnetic field, was successfully observed and recorded by J. J Thompson in 1913.[13] It was Sir Francis William Aston in 1920, who summarized and provided skeleton of today’s mass spectrometer. He described mass spectroscopy as a combination of sample inlet, ionization, mass analyzation and detection units.[12] During its early days, mass spectrometer utilized the direct sample injection method by using a simple interface to separate the inlet point from the vacuum chamber with minimum sample preparation and no prior chromatographic separation. However, direct sample inlet may affect the measurements parameters, the introduction of sample for mass analysis by using this method is quite fast.[11] One of the biggest advancements happened in the sample inlet system of mass spectrometer (MS) in 1960, when A. James and A. Martin, first interfaced gas chromatography (GC) with mass spectrometer, by using a packed column injection. After this invention, a Swedish medical scientist, Einar Stenhagen patented a high flow packed column with jet separator and a large bore capillary column of 530-750 µm inner diameter connected to the MS vacuum chamber. This advancement immensely changed the sample flow rate into the ion chamber. Integration of liquid chromatography (LC) column with MS in the 1970 solved one of the biggest concerns associated with GC-MS interface, where control of the sample flow rate and separation of carrier gas is troublesome and added extra steps during the mass analysis. Interfacing LC with MS was first attempted by Patrick Arpino and Fred Maclafferty in the early 1980. However, there is a debate that, it was Evans Hornings group of Baylor Medical School, who first successfully interfaced LC with mass spectrometer by using chemical ionization of the injected liquid sample before passing it to the ionization chamber. In the beginning of 1990, LC-MS flourished and drawn attention by most of the analytical chemists. In the modern LC-MS sample inlet system, capillary electrophoresis or electroosmotic flow or direct infusion of liquid via flow injection through <2mm capillary column is widely interfaced in between sample column and vacuum chamber of MS.[12] In online mass analyzation of liquid or gaseous sample by separating the injected sample from the vacuum lock with a porous membrane, was proposed by George Hoch and Basel Kok in 1963.[13][14] The teflon based membrane inlet system, later used in the sample injection process of the electrochemical reactions in the late 1970s, which created a new pathway for the electrochemists to analyze their reaction product on the electrode surface through MS.[14] Since the beginning, it was always a huge challenge for the analytical chemists to study the hydrocarbons in their elemental level by using mass spectroscopy, because of the lack of established sample injection of the hydrocarbon-based samples. In late 1997, a gallium covered frit of capillary pipet along with a secondary orifice mask, which creates a secondary protective layer for the frit inside the heated chamber, is used to inject most of the hydrocarbons up to C40.[15][16] In the beginning of the 20th century, a modern sample introduction device named as high-performance microchip, interfaced with MS to introduce the silicon oxide based or some other polymeric samples to the ionization chamber, was in its experimental phase in the laboratory. However, in recent days, microchip-based inlet system described as one of the highest velocity sample injection systems available.[17] Moreover, atmospheric sample inlet system made of stainless steel orifice leak is one of the oldest gaseous sample introduction methods which is very simple, rugged with moderate flow rate at atmospheric pressure without the need to use high pressure pump, which certainly reduces the installation cost.[18]

Sample Injection by GC and Capillary Electrophoretic Inlets[edit]

In order to attain the qualitative and quantitative characterization of the small fraction Gas chromatography (GC) samples, coupling of proper inlet system such as batch inlet and direct capillary or packed attachment of GC with the mass spectrometry, is considered to be one of the most prominent in modern day molecular spectrometry.  Inlet system of gas chromatographic samples into mass spectrometer can be subdivided into batch inlet and column-based insertion which mainly varies upon the volume of sample. Basic principle of the batch inlet of GC samples into the ionization chamber is to vaporize the introduced sample into large expansion volume and carry the expanded samples through a molecular leak system in to the MS chamber. The suitability of this process evidently depends upon the availability of the sample volume and the flow rate of the carrier gas. The rate of molecular leak and size of the expansion volume influences the adaptation of the batch inlet system with the mass spectrometer.[18][19] In order to withstand the high temperature operation during the expansion of the inserted sample, the inlet is constructed by using a stainless-steel chamber. Sample of 10-8-10-10 gm from GC column can be easily injected to MS chamber by using this batch inlet system.

By varying the molecular leak with sample size an optimum mass spectrum can be obtained in micro gram level. Moreover, the retained sample in the mass analyzer, injected by batch inlet system can be reclaimed to reuse if required. Figure 01 depicts this successful and highly efficient sample injection method which comprises a vacuum valve B, a quit fit vacuum connector C along with a micrometer valve E. Most often sample is injected through the port D, where silica matrix is added, and direct sample analysis could be done. The whole assembly could be wrapped with an insulating cover when excessive heating is required to vaporize the sample. Depending upon the volatility nature of the introduced sample, they can be frozen before pumping through the auxiliary vacuum A. Room temperature sample analysis can also be carried out through this inlet methods, in case of thermally unstable samples by keeping the micrometer valve E open, which facilitates the moderate sample flow into the ionization chamber.[19][20][21][22]

Due to the inconvenience in sample collection and separation methods for complex gas mixtures, in batch inlet method, a more sophisticated, useful and high-performance direct sampling by packed and capillary column have been introduced.[23][24][25] In figure 3, packed and capillary column sample inlet systems, which utilizes two basic injection phenomena, have been depicted.  In the first type ‘A’ for both capillary and packed column, the analyte is collected and injected through an exit slit system into the mass analyzer. However, in this method, heavy loss of injected sample, limited its versatile use in the modern chemistry world. To overcome this problem, the use of molecular separator, in place of exit slit, has shown some promising impacts. In figure 4, a simple beiman type separator is presented. Here, ‘I’ is the sample introduction port of gas separator from the capillary column, which drives the gaseous sample into the glass fritz towards section ‘A’, the injection port of sample into mass analyzer through a pressure reducer ‘G’. Sample and analytes that do not diffuses through the injection port ‘A’, just pumped out via port ‘D’, which is mainly used to screen out the residual gases, such as mixed carrier gas with the sample. Restriction valve ‘B’ controls the sample flow from port ‘I’ through the cylindrical glass tube towards the mass analyzer.[18][19]

LC Based Sample Injection[edit]

LC-MS is one of the most efficient liquid and less volatile sample analysing techniques available in the branch of analytical chemistry.[26] The efficiency of the technique is highly dependent on the type of instrumentation assembled during the sample introduction. Usually a narrow bore packed column made of silica (figure 01), mounted on a moving belt through the vacuum lock to the ion source, is found to be an ideal set up to introduce the liquid samples into the mass spectrometer with the amalgamation of the liquid chromatography.[27][28]

The major advantage of using LC-column based inlet system into the mass spectrometer, is that, this technique eliminates the requirement of using high pressure vacuum pump and hence reduces the cost by a margin. Thermally labile samples, which are separated by liquid chromatography are passed through a packed column and deposited onto a moveable belt, which is mainly a metal wire or made of plastic. While the drive ruler drags the belt along with the sample into the tunnel seals to vacuum lock, most of the solvent used in the liquid chromatography are selectively and thoroughly removed. After the removal of the solvent, neutral sample molecules thermally desorbed and flash heated on the moving belt. While flash heating removes the moisture, retained sample on the moving belt pass through the heating chamber where thermal desorption, using either electron impact or chemical ionization is carried out. In the final step, the left-over samples along with other residues which are not vaporized and pyrolyzed during heat treatment, are mechanically wipe out in order to regenerate the working or moving belt cycle for the next sample injection. In order to achieve the maximum injection efficiency of the non-volatile sample, which is ensured by complete ionization of the injected solution, vacuum pump pressure, temperature of the packed column, pumping speed and volatility of the sample should be studied very carefully.[27][29] Usually, by using a LC based packed column mounted on a moving belt with a moderate vacuum pressure, sample injection speed of 10-60 µl/min can be achieved. In modern day LC based inlet system, most often packed column is attached to a post column stream splitter to control the overflow of the solution into the ion chamber.

However, one of the major challenges of using this sample injection system is, while injecting the volatile solvents into the high vacuum lock, premature solvent evaporation and precipitation of the impurities on the ionization chamber might occur. In order to overcome this problem, a pinhole aperture of 5 µm diameter with high kinetic energy liquid jet inlet is used. This high energy jet inlet controls the gas flow in the ionization chamber and prevents the sample into premature evaporation.[28]

Electrokinetic Inlet System[edit]

Differential electrochemical mass spectrometer (DEMS) with electrochemical cell attachment via Teflon membrane, rotating electrode inlet or pinhole inlet to introduce the sample into the vacuum lock, is found to be one of the most efficient mass spectrometric sample injection methods. This inlet system helps the immediate quantification of electrochemical reaction products in brief time after their formation.[30] This method is found to be very sophisticated as the amount of product produced after the electrochemical reaction which further injected to the mass spectrometer, is very small. In order to detect this small quantity via mass spectrometer, proper inlet system needs to be selected, which will ensure the maximum sample input into the ionization chamber through the vacuum lock.[31][32]

Because of their non-porosity and hydrophobic nature, a Teflon membrane placed in an electrochemical cell which separates the electrolytes and reaction chamber from the vacuum lock of the ionization chamber (figure 6).

Figure: Representation of a Teflon membrane separated electrolyte[33]

Usually, product generated by the electrochemical reaction on the electrode surface in solution is transferred to the mass spectrometer from electrolyte phase through the high-pressure vacuum chamber. The electrolyte phase is separated from the vacuum chamber by using hydrophobic teflon membrane which is only permeable for the volatile molecules. Although, liquid does not penetrate through the membrane pores, dissolved gases and other thermally labile molecules can easily pass through within less than 0.8µm pores. Thickness of the teflon membrane highly depends upon the surface tension of liquid as well as critical contact angle between liquid and membrane. Normally pore width of 0.1-20 nm with 75 µm thick teflon membrane is quite useful for many of the volatile samples.

In conventional differential electrochemical mass spectrometer (figure 7), glass supported cell body along with teflon tube fitted with steel fritz connected to the vacuum chamber, is widely used.[34] The use of teflon tube has an advantage of continuous forced convection of the volatile samples in large range, to the high vacuum chamber. Moreover, rotating disc electrode which is considered to be a classical mass transport technique in electrochemistry, can also be used as an inlet system for the DEMS. A 100 nm thin sputtered platinum electrode attached with the teflon membrane at high rotation speed can be utilized as a solution-based mass inlet system with a maximum 95% sample transfer efficiency into the ionization chamber.[30][34]

Membrane Inlet[edit]

Membrane inlet mass spectrometry has become one of the most profound mass analysis techniques, which basically characterizes the stable isotope distribution of gases by using a gas permeable membrane that enables the ingress of gaseous molecule into the ionization chamber of the mass spectrometer. Membrane inlet (MI) is quite straightforward yet durable sample injection technique, which utilizes the labelling of individual isotopic gaseous molecules in order to track down the isotopic exchange rates. The understanding of the isotopic exchange rate will help the researchers to understand the chemical properties, such as flow rate and adhesion of the molecule. Online isotopic fractionation while injecting the gaseous sample along with its high sensitivity and simplicity of instrumentation, established membrane inlet system is cited as one of the most convenient sample injection methods to study various reaction mechanisms.[35] Study of various isotopes by using mass spectrometer was first introduced by Thompson in 1913, who at that time figured out two different trajectories of mass while observing the stream of Ne+ ions passing through the electromagnetic field. Mass spectrometry detects the individual mass to charge ratio of molecule by ionizing them at the high vacuum, which minimizes the probability of collision between gaseous molecules. As a result, gaseous sample introduction into this high vacuum system is happened to be very challenging and to overcome this issue a membrane was installed to separate the injected sample from vacuum lock before passing the sample to the ionization chamber.

A permeable and semipermeable membrane accompanied by a magnetic stirrer to eliminate the formation of boundary layers on the membrane, is considered to be the fundamental part of membrane inlet system.[36][37] Depending upon the type of sample and the desired sensitivity, the attached membrane could be 10-100µm thick and 0.5-2 cm in size. To ensure the stability of the membrane and thwart the probability of the internal collapse, a porous plastic sheet or thin metal film containing fine holes is binded to the membrane. A cryogenic filter affixed at the interface of the membrane and ion chamber removes the presence of water vapour. Sample injection through the membrane inlet comprises of three basic steps: In the beginning, injected sample got adsorbed on the membrane surface followed by a successive entry of the target molecule, which are then passed through the high vacuum lock through the membrane pore to reduce the internal collision and in final step, high pressure vacuum pumped molecule enters into the ionization chamber.[35]

Membrane inlet mass spectrometry (MIMS) is a technique for the rapid analysis of volatile organic compounds in aqueous solution, this approach is well established.[38] Sample introduction through membrane has broadened the analysis of compounds which were hitherto out of reach.[39][40]. The fundamental character of this method of sample inlet is fast response, ease and sensitivity, which is usually used in collecting data from composite sources such as pharmaceutical products, environmental specimens, biomarkers.[40]

Preparation of sample is not required, though dense or turbid solutions are filtered and slight adjustments are made such as pH on-site or before the experiment.[41] The liquid or gaseous streams are then passed through a semipermeable membrane, which introduces the existent compounds in the matrix into the mass spectrometer. The quantity of the stream depends on the vapor pressure of the analyte, rate of diffusion and solubility in the membrane material.[42]

Polymers of silicon are usually used for the membrane, generally about 0.12mm thick. Separation of analytes from an aqueous solution into vapor phase is done through pervaporation.[43] This process can be split into three steps:

  1. The selective assimilation of analyte at the surface of the membrane.
  2. Permeation through the membrane and
  3. Desorption into vacuum, or into a gaseous carrier stream.[44][45]

There are other substitute polymer membranes that have been tested including latex, Teflon, polyimide and nitrile sheet polymers, that are in 13-125µm thickness extent. The rate determining step is usually the diffusion through the membrane, this also applies to transport of gaseous samples through the membrane.[46]  

The achievement of MMIS can be evaluated by four elements: (i) The quickness with thich permeation is attained (ii) The total ease of analyte passing through the membrane (iii) The separation factor(selectivity) α (iv) The enrichment factor β.[47]

Direct Injection of Sample with High Efficiency Nebulizer[edit]

In recent days, direct sample injection with high efficiency nebulizer attached with inductively couple mass spectrometer has become one of the prominent sample introduction methods to the ionization chamber.[48] Sample introduction efficiency of 1-100 µl/min without the use of high-pressure pump, DIHEN technique offers a comparatively low cost and easy sample handling system.[49] In comparison with direct insertion probe and direct injection nebulization techniques, DIHEN provide some extra benefits:

  1. as DIHEN, does not use spray chamber to inject samples into the ionization chambers, there is minimum chance of volatile sample loss.
  2. Probability of injecting interfering materials during sample injection is quite low, which ultimately improve the signal to noise ratio in the detection system.
  3. Introduction of sample volume is higher.
  4. Well suited method for the injection of petroleum products.[50]
Schematic diagram of Direct injection high efficiency nebulizer.[51]

DIHEN is basically constructed from the borosilicate glass attached with a nebulizer tip dimension which is also used in other nebulization-based sample injection methods. A capillary tapper which is attached with the nebulizer is fitted with Teflon based capillary tube with dimension of 0.008x0.0016 inch, plays a vital role in reduction of the dead volume in the nebulizer. Capillary is basically supported by a glass tubing which reduces the possible chances of sample capillary damage due to the oscillation of the nebulized gas. The reduction in the dead volume ultimately minimizes the memory effect in the capillary column. Connection of nebulizer with the carrier gas chamber is equipped with a micro flow injection valve which allows the argon or oxygen gas to carry the sample. A metal free injection valve with six port, actuated by a computer control system, controls the sample injection and load into the ionization chamber.[52]

Microfabricated Inlet System[edit]

Fast assays with high-throughput of subpicomolar size of proteins, peptides, DNA and various small molecules, is now essential for development of drugs, environmental studies among other researches.[53] Microfabricated devices have the means to control the direction, circulation and detection of minuscule amount of analyte.[54] Notwithstanding their miniature  size, the microdevices have a huge potential for use in biological mass spectrometry,[55] they are expected to be a critical part in the advancement of high throughput instrumentation, the extensive element of miniaturization rests in high-speed, decreased sample size and reagent expenditure.[56][57]

Coupling of microfabricated devices to electrospray ionization mass spectrometry has been introduced in recent years. The initial designs focused mainly on the sample manipulation on the chip and also off-chip infusion with electrospray sample ionization, other analytical operations besides sample infusion has been done on the chip.[58] Attachment of microfluidic devices to mass spectrometer which employs either electrospray ionization or matrix-assisted laser desorption or ionization connection continues to be a challenge for a number of reasons;[59] First, the manufacture of high performance microchip-integrated electrospray emitter can be done only by utilizing specially designed microfabrication approach that work well primarily in silicon or polymeric substrate.[60][61][62] Second, alternative fluid propulsion mechanisms application that generates fluid flows suitable with mass spectrometric detection, such as pressure-driven approaches,[63][64] electrochemical induced transport,[65] or centrifugal dispensing[66] have been researched only in recent times and these methods are not used extensively.

The manufacture of microfluidic devices involves similar steps developed in the production of semi conducting devices . Generally about a few cm2, these devices can be manufactured from an assortment of substances such as glass,[67] quartz,[68][69] silicon,[70][71] and polymeric substrates.[72] The selection of the appropriate material depends on its production ease, properties of the surface and cost.[73] However, care must be taken in choosing a material that has enough chemical stability to avoid the development of analyte adducts from the device intrinsically.[73] The most commonly used process to produce microfabricated devices depends on transferring a pattern onto the surface of a desired substrate by photolithography and the subsequent removal of the defined matter by wet chemical etching in liquid phase, or dry etching in a gas-phase plasma. Another way involves deposition of metal on given substrate and silicon dioxide on silicon substrate.[74] Lastly, casting, molding, laser machining can be used for polymeric materials.[73][74]

In microfabricated devices, flow of fluids is in the order of 0-300 nL/min, this is equivalent to the flow rates essential to operate micro/nano electrospray ionization sources.[75] To date, electrospray from microfabricated devices has been created precisely from the chip surface[76][77] or using popular nano/microspray, liquid sheath, and liquid junction connections.[78][79]

Critical concerns that must be discussed in the design of a microchip-MS connection are: first, a concept must be created to certify that high ESI efficiency from the microfabricated device, to obtain high sensitivity. Second, if separation is required on the chip, input of the connection to the band broadening must be reduced.[80]

Direct Probe Inlet[edit]

This involves the use of a probe or sample holder to insert non-volatile liquids or solids into the ionization region, which is infused through a vacuum lock.[81] The vacuum lock is constructed to curb the amount of air that will be drained from the system after the probe is inserted in the ionization region.[81][82] The probe is located very close to the ionization source and the opening leading to the spectrometer, and the sample is placed on the glass surface or aluminium capillary tube.[82]

The proximity of the sample to the ion source of ionization and the nominal pressure in the ionization area allows collection of spectra of thermally unstable molecules before occurrence of decomposition.[82] There is also an increased concentration of the comparatively non-volatile compounds because of the low pressure.

In the research at Scientific instruments services, the sensitivity of the Agilent 5973/5975 was shown to be astounding when used with the direct probe and limit of detection down to 1.0ng.[83]

A major merit of the probe is that small amount of sample volume is required. The probe is furnished with a heater to volatilize the sample.[83] Employment of probe allows the study of non-volatile materials such as steroids, carbohydrate, polymeric substances of low molecular weight.[84] The major sample condition is reaching an analyte partial pressure of at least 10-8 torr ahead of the beginning of decomposition.[85]

An adaptation of the direct probe inlet is the desorption chemical ionization probe, in this case the probe tip is designed in the form of an incandescent platinum filament [83]. It evaporates and partially ionizes when the substance is heated.[86]

Atmospheric Pressure Inlet System[edit]

Interferences such as fragmentation in chemical reactions, makes it difficult to identify intermediate free radicals and species. This problem motivated scientists to create an effective mass spectrometer to quickly identify species in the chemical reactions. Fiji et al[86] created an effective inlet system which functions as a juncture between the samples at atmospheric pressure and the high vacuum in a mass spectrometer. They proposed and built up a novel approach which depends on a soft ionization lithium ion attachment process connected with a mass spectrometer (Li+MS).[87]

However, they were unable to introduce analytes directly into the apparatus at atmospheric pressure, which led them to create a unique atmospheric pressure sampling inlet system that doesn’t need a differential pumping stage.[87] The features considered in developing this inlet system includes chemical inertness of the surface of the inlet, ability to endure temperatures as high as 1000K for a long duration and higher temperatures for a short duration, response time of less than 0.1s and addition of minimum perturbation to the flow of gas into the mass spectrometer.[88]

General overview of atmospheric pressure inlet system attached to a Li+ ion mass spectrometer. RC – Reaction Chamber; ELS – Electrostatic Lens System; QMS – Quadropole Mass Spectrometer. Adapted from reference.[89]

The atmospheric pressure inlet system consists of an aperture leak set up to provide a constant and smooth analyte introduction into the mass spectrometer, the conflat flange connects the atmospheric pressure inlet system to the reaction chamber of the mass spectrometer in a way that the aperture is located close to the Li+ ion emitter about 5mm.[88]

This design allows a consistent analyte leak into the Torr range, and undisturbed flow from the atmosphere to the mass spectrometer.[90]

All Glass Heated Inlet System[edit]

In the analysis of high molecular-weight compounds, higher temperature is required to vaporize the large molecules, the all-glass inlet system was devised to satisfy this condition.[91][92] Important characteristics of glass inlet system includes a special sample vacuum lock which allows fast introduction of accurately measured amounts of either solid or liquid samples without losing the vacuum in the spectrometer source.[92] A durable magnet-controlled glass ball type valve is used with an effective leak rate.[93]

Weighed samples are placed in the vial, solid samples are placed into small boats and liquid samples are measured by volume in precision-bore capillary tubing, with one end closed [90]. The little load of gas which is trapped in the capillary moves the sample out after transporting into the heated inlet system where vacuum is applied.[94]

All-glass heated inlet system is only appropriate for solids with high vapour pressure. All-glass heated inlet system can be applied to high boiling impurities using manual temperature programming. It is also used for identifying vapours evolved from Sulphur-based paints at high temperature.[94]

Future Perspectives[edit]

Sample inlet system modification and advancement have come a long way but has still not attained its true potential, that is inlet systems with high stability, low limit of detection and high selectivity among other parameters. The future of this area will entail out of the box thinking in both the design of the system and the analytical methodology. Extra customization is a crucial target for instrumentation, but with elevated stability of the system to help from results that are reproducible and certified methods of analysis.

The fast advancements of microfluidics are influencing the bioanalytical world. The latest techniques and inventions can be followed in professional journals such as “Lab on chip”, or dedicated issues of well-established periodicals.[93] There are other current review articles that give clearer pictures of latest trends and future perspectives of the field.[94] Continuous advancement is happening in the field and marketing of new micro-devices as inlet systems merged with MS will be available on a commercial scale.

Lastly, for future perspective, all the units around the sample inlet system needs to be focused on to make improvements on the presently available ones. Improvement in reproducibility, high throughput, reliability and effective sample techniques are all important in creating and advancing on sample inlet systems.


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