CZ308396B6 - Automated multichannel pressure pulse modulator - Google Patents

Abstract

An automated multi-channel pressure pulse modulator (1) comprising a carrier gas inlet (10) to the modulator (1), shut-off valves, connectors for connecting modulating valves (21), a valve switching relay and a single electronic control interface for controlling at least two pairs of electronic pressure regulators for at least two simultaneous analyzes, the electronic pressure regulators are connected through the outlets (14) of the carrier gas (10) to at least two corresponding pairs of modulating valves (21), each modulating valve (21) is connected by a capillary ( 22) with a three-way connecting element (23); between the pair of modulating valves (21) connected by the three-way connecting elements (23) there is a storage loop (28) between the primary column (24) and the secondary column (25) from the respective set of columns that the secondary column (25) of each of the at least two mutually independent sets of columns is connected to its own detector (27). Optionally, the primary column (24) of each set of columns is also connected to its own injector (26).

Description

Automated multichannel pressure pulse modulator

Field of technology

The invention falls within the field of apparatus and equipment for performing chemical analysis of samples, in particular control systems for ensuring the flow of a carrier gas, as one of the instruments for performing two-dimensional gas chromatography.

Prior art

Today, a large number of chemical preparations or chemical substances are produced and used in the world, which are used in various industries, such as petrochemistry, food industry, cosmetics or pharmacy. The quality and production of chemicals, food, medicines and cosmetics are often controlled and regulated by the relevant authorities (eg petroleum products, allergens in food, amount of active substance in medicines, pollutants in water, etc.). This places demands on the high quality of the determination, on the development of methods for the determination of new substances, and, in addition, on the growing number of analytes and components of which the sample is composed. Real samples, such as natural essential oils, petroleum products, biological samples and environmental samples, can contain up to thousands of substances. Determination of all macro and micro components of such a complex sample using classical gas chromatography (one-dimensional GC, 1D-GC) can be insufficient, problematic and sometimes impossible. Due to their similar properties, some substances cannot be separated from each other during one analysis and others cannot be separated at all.

For this purpose, separation systems with higher efficiency (peak capacity) and selectivity of determinations have been developed. The use of multidimensional separation techniques, such as the "heart-cut" technique, has proven to be a possible solution to this problem. This allows the critical part of the sample to be separated on another column with a different selectivity after incomplete separation on one column. This method, with many others, belongs to the group of gas chromatography (GC), namely two-dimensional gas chromatography (2D-GC). However, the overall efficiency of these methods, expressed in peak capacity, did not differ significantly from the efficiency of conventional one-dimensional gas chromatography (1D-GC), as only a small portion of the sample was subjected to two-dimensional analysis. Most of these methods have certain shortcomings, such as the heart-cut method showing shifts in retention times depending on the number and length of heart-cuts. For these reasons, other more suitable solutions were sought and the so-called comprehensive GC (GCxGC) proved to be one of the possible solutions.

Comprehensive two-dimensional gas chromatography (GCxGC) was defined as an analytical technique of gas chromatography by Professor Phillips and his student Zaiya Liu in 1991.

This technique uses two different columns with different stationary phases (separation mechanism) in series. In GCxGC, the primary column in the first dimension is usually of the dimensions used in conventional gas chromatography, while the secondary column in the second dimension is shorter and of the dimensions used for fast GC. A modulating device (modulator) is then placed between the columns. During the analysis, the effluent from the first dimension (primary column) is captured by the modulator and then reproducibly rapidly metered into the second dimension (secondary column). This process achieves a retention plane of separation on the first and second dimensions. Using this system, the resulting theoretical peak capacity (efficiency) is given by the product of the peak capacities of each column, which means an increase in peak capacity (efficiency) by several orders of magnitude. E.g. When comparing the GC-MS and GCxGC-MS methods on analyzes of blood serum samples in an article published by Winnik J. H. et al., three times more substances were detected by the GCxGC-MS method than using classical GC-MS.

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Modulators that are currently known work on several principles, for example a thermal modulator or a pressure modulator. The function of the modulator can be divided into basically three processes:

1. continuously collecting a small fraction of the effluent from the ID, thereby ensuring that the separation is maintained in this dimension;

2. focusing or refocusing the effluent in a narrow band;

3. rapid transfer (dosing) of the fraction of collected and focused effluent to the second dimension.

These three steps are called the modulation cycle, which is repeated periodically during the chromatographic run. The time required to complete the entire cycle is then defined as the modulation period, which is usually between 2 and 10 seconds.

An example of one of the first thermal modulators is the so-called "Sweeper", which contained a short capillary inside coated with a thick layer of stationary phase film, where the effluent analytes from the primary column were retained, accumulated and transferred to the secondary column. Rapid desorption of analytes was achieved by heating the capillary with a rotating slit heater.

Today, the most used thermal modulator is the cryogenic modulator, which is commercially available and which is most often used for its high modulation efficiency (dosing). Its main advantages include the ability to produce very narrow peaks in the chromatogram (peak width in the middle of its height less than 100 ms), which are necessary to achieve a high overall efficiency of the GCxGC system. Cryogenic modulators have several different design solutions, eg a sliding cryogenic modulator.

Such a cryogenic modulator can operate, for example, on the principle of two jets, where cooled nitrogen gas and alternately warm air are permanently supplied by the nozzle to a short section of the capillary loop connecting the two separation columns. Cooling of a portion of the capillary retains the effluent analytes from the first dimension at this point, and after heating, rapid dosing into the secondary column occurs. However, these modulators are costly due to the high purchase price, the high consumption of refrigerant (liquid nitrogen) and the relatively large investment in cryogenic vessels.

The most significant problem of the cryogenic modulator is its acquisition and operating costs, which are a major obstacle to the introduction of the GCxGC method into wider practice.

With the development of cryogenic modulators, cheaper alternatives to modulators based on other principles were developed at the same time. Examples are pressure modulators, which can be divided according to the basic principle of operation into three types: "Microfluidic Deans switch" modulators, "differential flow" modulators and pressure pulse (fluid) modulators. By comparison, the carrier gas consumption for a pulsed pressure modulator is more than 100x lower compared to a cryogenic modulator. In the literature we can find a wide application of the use of pressure modulators as cheaper alternatives to cryogenic modulators in the analysis of eg petroleum derivatives such as gasoline, kerosene or diesel, essential oils, perfumes and fragrances, as well as biological and environmental samples.

This is an approach based on external / internal valves, where differential flows are used to fill and flush the storage loop for the sample effluent. The essence of the pressure pulse modulator is the rapid dosing of effluent fractions from the primary column to the secondary column by means of carrier gas pressure pulses. The advantage of this modulator is the high efficiency of analyte capture and dosing without loss of sample to the secondary column. The advantage is also a relatively simple design solution and low acquisition and operating costs. The disadvantages are higher flow rates

-2 CZ 308396 B6 volumes of gas at the outlet of the secondary column, which limits its use in combination with a mass detector. Compared to the cryogenic modulator, the disadvantages are: production of wider peaks (width in the middle of the peak height above 100 ms), larger dead volumes of connecting parts of the modulator between columns which causes washing of the peaks and thus their insufficient distribution up to the baseline chromatogram. However, all these disadvantages are not fundamental and can be minimized.

The closest prior art is a manual pulse pressure modulator, exemplified in STON, M. et al .: IMPROVED FLOW MODULATOR CONSTRUCTION FOR GC X GC WITH QUADRUPOLE MASS SPECTROMETRY; JOURNAL OF CHROMATOGRAPHIC SCIENCE, 2016 or in STON, M .: DEVELOPMENT AND OPTIMIZATION OF A ROBUST PRESSURE MODULATOR FOR MULTIDIMESIONAL GAS CHROMATOGRAPHY, DISSERTATION WORK, 2016, which precedes the modulator which is the subject of this application. The basic element of the instrumentation of the original modulator is a fast three-way valve, to the input of which the carrier gas (mobile phase) is supplied. The timing of the valve switching is controlled by the pulse generator control unit so that for a very short moment (pulse time, in the order of hundreds of milliseconds) the gas passes through a capillary marked "Auxiliary capillary 1" and for the remainder of the modulation period. ) the gas passes through a capillary marked as "Auxiliary Capillary 2" (of the order of seconds). Throughout the analysis, this process is then repeated cyclically in each modulation period. The "storage capillary" here serves as a storage space for the eluting fraction from the primary column, which is subsequently metered in by the increased gas flow caused by the pressure pulse from the Auxiliary Capillary 1 to the secondary column. The auxiliary capillary 2 is primarily intended to supply the secondary column with mobile phases.

For this model, it is necessary to set / regulate the pressures manually, with an accuracy of ± 10 kPa. When comparing the efficiency of the modulator with the cryofocus modulator, the average repeatability of the retention times (relative standard deviation) for the pulsed pressure modulator was approximately 2.0% versus 0.5% for the cryofocus modulator and peak areas approximately 3.5% versus approximately 1.0% for the cryofocus modulator. The cryofocus modulator is more robust and efficient, but based on the comparison, it can be said that the pulse pressure modulator represents a full-fledged modulation tool when all parameters are set correctly. The great advantage of the original modulator compared to the cryofocus modulator is its very low purchase price and almost zero operating costs.

The documents describe an instrument containing only one set of columns, but does not solve design and practical problems associated with GCxGC technology such as column replacement in a GCxGC system, where after such an intervention in the system it is necessary to re-optimize the whole system for further measurements. The modulator described in the mentioned documents is further only equipped with manual pressure regulators regulating the pressure of the gas entering the auxiliary capillaries. Thus, the method performed on this modulator allows only coarse pressure adjustment and does not allow compensation of the change in gas viscosity during the measurement caused by the temperature gradient applied during the analysis, which leads to reduced measurement accuracy and practically does not allow more than one set of columns to be used. .

Embodiments comprising one primary and more secondary columns are also known, for example according to US 2010154511 A1 and WO 2013070954 A1. In this solution, the effluent leaving the primary column is distributed by an electronically controlled valve to one of the secondary columns. Thus, this assembly with respect to only one primary column does not allow two or more simultaneous analyzes to be performed. The documents further do not mention the possibility of controlling the pressure of the gas injecting the fraction into the secondary columns.

It is therefore an object of the invention to provide a modulator enabling multiple simultaneous analyzes to be performed in order to reduce the time required to perform the analyzes while increasing the accuracy of the measurements.

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The essence of the invention

The essence of the invention is an automated multi-channel pressure pulse modulator, which eliminates the shortcomings identified in the prior art, in particular the design and practical problems of known modulators.

The modulator is equipped with control electronics connected to a computer with control software, at least two pairs of electronic pressure regulators and is able to control the switching of at least two pairs of valves, which allows its easy use in combination with GC having at least two injectors and thus provides at least two simultaneous analyzes sample under different analysis conditions (for example, different separation conditions or choice of detector). This allows two or more analyzes to be performed simultaneously on separate sets of columns, but does not limit the use to perform multiple sequential analyzes without having to replace the set of columns if the column set installed in the first channel is unsuitable for analysis and only switches to the second or each additional channel with its own set of capillary columns. This greatly simplifies or even eliminates the necessary optimization process associated with column replacement over the prior art.

The automated multichannel pressure pulse modulator further solves the shortcomings of the especially known manual pulse pressure modulator according to the state of the art by allowing to set and regulate the pressure with a deviation of ± 2 kPa from the set value, which it maintains by automatic control. With the known modulator according to the state of the art, it is necessary to set and regulate the pressures manually, when an insufficient accuracy of ± 10 kPa was achievable.

The average repeatability of the retention times, expressed as their relative standard deviation, was approximately 2.0% for the known modulator according to the prior art, while for the modulator according to the invention <0.3%. In the case of the prior art cryofocus modulator, the standard deviation of the retention times is approximately 0.5%. This equates to an automated multi-channel pressure pulse modulator with a cryofocus modulator, which is, however, significantly more expensive to acquire and operate.

Explanation of drawings

Figure 1 shows a diagram of a modulator assembly according to an exemplary embodiment of the invention.

Figure 2 shows a diagram of a modulator assembly with connected columns according to an exemplary embodiment of the invention.

Examples of embodiments of the invention

A preferred embodiment of the automated multi-channel, in this example two-channel, pulse pressure modulator 1 consists of carrier gas inlet 11 to modulator 1, shut-off valves 12, four electronic pressure regulators 13 for regulating gas inlet and outlet pressure, carrier gas outlet 14 from pressure regulators 13 to the respective switching modulating valves 21 for modulation, i.e. filling and flushing the storage loop 28 for effluent from the primary column 24, connectors 15 for connecting the modulating valves 21 for modulation, communication port 16 for connection to PC, instrument fuses 17, 12Vdc supply 18 modulator, switches 19 for switching on / off modulator 1, solid state relay 111 for switching valves, light signaling 112 of valve operation and modulator 1, and further electronic control interface 110 of modulator 1, which is controlled by software in connected PC for setting controller selection 13 to be used, pressure on electronic pressure

-4 CZ 308396 B6 regulators 13 and pressure changes over time, and further setting which valves 21, in which relative order and at what time will be closed.

The automated two-channel pressure pulse modulator thus assembled is in this case connected in an assembly with two mutually independent columns, as follows.

Switched valves 21 are connected to the outlets 14 of the carrier gas 10 from the pressure regulators 13, which are always connected in pairs by auxiliary capillaries 22 to three-way connecting elements 23, which together form an intermediate link between the primary column 24 and the secondary column 25 from the respective set of columns. a loop 28. An injector 26 is always connected at the inlet to each primary column 24 and a detector 27 is always connected to each outlet at the outlet.

Industrial applicability

The invention is industrially applicable in the analysis of chemicals, foods, drugs or cosmetics for the purpose of determining the composition of analytes, determining the quality or preparation of new substances.

Claims (2)

PATENT CLAIMS An automated multichannel pressure pulse modulator (1) comprising a carrier gas inlet (11) (10) to the modulator (1), shut-off valves (12), connectors (15) for connecting modulating valves (21) and a relay (111) for switching valve, characterized in that it further comprises a single electronic control interface (110) for controlling at least two pairs of electronic pressure regulators (13) for at least two simultaneous analyzes, the electronic pressure regulators (13) being connected through the outlets (14) of the carrier. gas (10) with at least two corresponding pairs of modulating valves (21), each modulating valve (21) being connected by a capillary (22) to a three-way connecting element (23), with three-way connectors connected to the pair of modulating valves (21). the connecting elements (23) is a storage loop (28) between the primary column (24) and the secondary column (25) of the respective set of columns, the secondary column (25) of each of at least two mutually independent sets of columns being connected to its own detector and (27). Automated multichannel pressure pulse modulator (1) according to claim 1, characterized in that the primary column (24) of each set of columns is connected to its own injector (26).