阅读说明：本技术 改进的热调制器 (Improved thermal modulator ) 是由 W·W·卡森 A·克罗蒂 M·塞尼 R·塔什尼 于 2019-03-19 设计创作，主要内容包括：本发明公开了一种用于气相色谱法的改进的热调制器(2),其包括：﹣分析毛细管(4),其将由分析物穿过并且旨在插置在两个气相色谱柱(1,3)之间；﹣包括冷区(10)的冷却系统(8)；﹣支撑元件(11),其与所述冷区(10)相关联并且构造成支撑所述分析毛细管(4)的一部分(17),使得所述部分(17)处于相对于所述冷区(10)的温度处于基本上对应或略高的温度,所述分析毛细管(4)的所述部分(17)穿过所述支撑元件(11)和/或与所述支撑元件接触,从而限定捕集部分(17),穿过所述分析毛细管(4)的所述分析物旨在被捕集/固定化在所述捕集部分中；﹣控制装置(14),其选择性地控制将脉冲电流向与所述分析毛细管(4)相关联的导电元件(70,71)的发送,以加热所述捕集部分(17),从而引起先前固定化的分析物的释放/解吸；﹣加热装置(80),其引起对所述分析毛细管(4)的部段(81)的加热,所述部段位于所述支撑元件(11)的外部并且在所述分析毛细管的穿过和/或接触所述支撑元件(11)的所述捕集部分(17)的上游,以使包含在所述部段(81)中的气体沿所述分析毛细管(4)的伸展方向快速膨胀,从而有利于已释放/解吸的分析物朝向所述捕集部分(17)的出口的推进。(The invention discloses an improved thermal modulator (2) for gas chromatography, comprising: -an analytical capillary (4) to be crossed by the analyte and intended to be interposed between two gas chromatography columns (1, 3); -a cooling system (8) comprising a cold area (10); -a support element (11) associated with said cold zone (10) and configured to support a portion (17) of said analysis capillary (4) so that said portion (17) is at a substantially corresponding or slightly higher temperature with respect to the temperature of said cold zone (10), said portion (17) of said analysis capillary (4) passing through and/or being in contact with said support element (11) so as to define a trapping portion (17) in which said analyte passing through said analysis capillary (4) is intended to be trapped/immobilized; -control means (14) to selectively control the sending of a pulse current to the conductive element (70, 71) associated with said analysis capillary (4) to heat said trapping portion (17) so as to cause the release/desorption of the previously immobilized analyte; -heating means (80) to cause heating of a section (81) of said analysis capillary (4) external to said support element (11) and upstream of said trapping portion (17) of said analysis capillary passing through and/or in contact with said support element (11), so as to cause a rapid expansion of the gas contained in said section (81) along the development direction of said analysis capillary (4), so as to favour the advancement of the released/desorbed analytes towards the outlet of said trapping portion (17).)

1. An improved thermal modulator (2) for gas chromatography, characterized in that it comprises:

-an analytical capillary (4) for traversing an analyte and intended to be interposed between two gas chromatography columns (1, 3),

-a cooling system (8) comprising a cold area (10),

-a support element (11) associated with said cold zone (10) and configured to support a portion (17) of said analysis capillary (4) so that said portion (17) is at a temperature substantially corresponding or slightly higher with respect to the temperature of said cold zone (10), said portion (17) of said analysis capillary (4) passing through and/or being in contact with the support element (11) so as to define a trapping portion (17) in which said analyte passing through said analysis capillary (4) is intended to be trapped/immobilized,

-control means (14) to selectively control the sending of a pulsed current to the conductive elements (70, 71) associated with the analysis capillary (4) to heat the trapping portion (17) so as to cause the release/desorption of the previously immobilized analyte,

-heating means (80) for causing heating of a section (81) of the analysis capillary (4) external to the support element (11) and upstream of the trapping portion (17) of the analysis capillary crossing and/or in contact with the support element (11), so as to cause a rapid expansion of the gas contained in said section (81) along the development direction of the analysis capillary (4), so as to favour the advancement of the released/desorbed analytes towards the outlet of the trapping portion (17).

2. The thermal modulator according to claim 1, wherein the cooling system comprises a reverse Stirling cycle cooler (8).

3. Thermal modulator according to one or more of the preceding claims, characterized in that said cooling system (8) comprises a cold zone (10) associated with said supporting element (11) to define a cold group (12), said cold group (12) being in contact with said trapping portion (17) for trapping said analysis capillary (4) for cooling by conduction of said trapping portion (17).

4. Thermal modulator according to one or more of the preceding claims, characterized in that said cooling system (8) comprises a cold zone (10) having a flat surface coupled with a corresponding flat surface of said support element (11).

5. The thermal modulator according to one or more of the preceding claims, characterized in that the cold zone (10) of the cooling system (8) and/or the support element (11) are at least partially wrapped with a heat insulating material.

6. Thermal modulator according to one or more of the preceding claims, characterized in that said support element (11) is made of a thermally conductive metallic material and is electrically insulating at least at the surface of said support element.

7. Thermal modulator according to one or more of the preceding claims, characterized in that said support element (11) is made of a thermally conductive material and is electrically insulating at least on said surface.

8. Thermal modulator according to the preceding claim, characterized in that said support element (11) has a geometry so as to define an optimal heat exchange interface between the cold zone (10) of the cooling system (8) and the trapping portion (9) of the analytical capillary (4).

9. The thermal modulator according to one or more of the preceding claims, characterized in that said support element (11) has the shape of a pyramid or a truncated pyramid or a cone or a truncated cone or a disc.

10. The thermal modulator according to one or more of the preceding claims, characterized in that said support element (11) comprises a housing seat (13) for said trapping portion (17) of said analysis capillary (4).

11. Thermal modulator according to the preceding claim, characterized in that said housing seat (13) comprises a through hole formed in said support element (11) or comprises a surface groove.

12. The thermal modulator according to one or more of the preceding claims, characterized in that said analysis capillary (4) is constrained to said support element (11) by clamping means (60).

13. Thermal modulator according to the preceding claim, characterized in that said clamping means (60) comprise a body (62), preferably shaped as a plate, fixed to said support element (11) to keep said trapping portion (17) of said analysis capillary (4) in contact with said support element (11).

14. Thermal modulator according to the preceding claim, characterized in that said support element (11) has a configuration suitable for supporting said analysis capillary (4) to fix and hold said trapping portion (17) of said analysis capillary (4) in contact with said cold group (12), so as to allow said trapping portion (17) to be at substantially the same temperature as said cold zone (10).

15. The thermal modulator according to one or more of the preceding claims, characterized in that said conductive elements (70, 71) comprise:

-at least a first conductive element (70) for current input in contact with the analytical capillary at a contact area (74) located upstream or downstream of the trapping portion (17) passing through and/or in contact with the support element (11), and

-at least one second conductive element (71) for current output in contact with said analysis capillary (4) at a contact area (79) located downstream or upstream of said trapping portion (17) passing through and/or in contact with a support element (11).

16. The thermal modulator according to one or more of the preceding claims, characterized in that said first and second conductive elements (70, 71) comprise a portion of the same analysis capillary (4) made of conductive material and interposed between said at least one first conductive element (70) and said at least one second conductive element (71), said trapping portion (17) passing through and/or in contact with a support element (11) being at least partially defined by a section of said analysis capillary (4) interposed between said at least one first conductive element (70) and said at least one second conductive element (71).

17. Thermal modulator according to one or more of the preceding claims, characterized in that said conductive elements comprise at least two conductive elements (70, 71) associated with corresponding portions of said analysis capillary, said corresponding portions being external with respect to said support element (11) and upstream and downstream, respectively, with respect to a trapping portion (17) of said analysis capillary which passes through and/or is in contact with said support element (11).

18. The thermal modulator according to one or more of the preceding claims, characterized in that said conductive elements comprise at least two conductive elements (70, 71) associated with portions of said analysis capillary, said portions being defined at the inlet end and at the outlet end of said analysis capillary, respectively, at the interior of said support element (11).

19. Thermal modulator according to one or more of the preceding claims, characterized in that said conductive elements (70, 71) comprise capillaries of the same type of metal as said analysis capillaries (4).

20. Thermal modulator according to the preceding claim, characterized in that said at least one first conductive element (70) for current input and/or said at least one second conductive element (71) for current output comprise wire-like elements of conductive material welded in correspondence of contact areas (74, 79) defined respectively in an inlet section (72) and an outlet section (73) of said analysis capillary (4) passing through said support element (11) and/or contacting said trapping portion of said support element.

21. Thermal modulator according to one or more of the preceding claims, characterized in that said pulsed current sent to said conductive elements (70, 71) to cause the release/desorption of the previously immobilized analytes has an amplitude of about 10A-200A and/or a duration of about 0.1 ms-10 ms.

22. Thermal modulator according to one or more of the preceding claims, characterized in that said pulsed current sent to said conductive elements (70, 71) to cause the release/desorption of the previously immobilized analytes has a frequency of about 0.03 Hz-10 Hz.

23. The thermal modulator according to one or more of the preceding claims, characterized in that it comprises constraining means (75) for maintaining:

-contact of the at least one first electrically conductive element (70) with the support element (11) and with the first conductor element (7) for current input/output, and

-contact of the at least one second electrically conductive element (71) with the support element (11) and with the second conductor element (7) for current output/input.

24. The thermal modulator according to one or more of the preceding claims, characterized in that said conductive elements (70, 71) are connected to current generating means for generating an electric current for heating in a substantially continuous manner said trapping portion (17) of said analysis capillary (4) which passes through a support element (11) and/or is in contact with said support element, for regulating the temperature of said analyte trapped/immobilized in said trapping portion.

25. Thermal modulator according to one or more of the preceding claims, characterized in that said conductive elements (70, 71) are connected to current generating means for heating substantially continuously portions of said analysis capillary (4) external to said support element (11) and respectively upstream (19) and downstream (21) of said analysis capillary (4) passing through the support element (11) and/or said trapping portion (17) in contact with said support element, so as to prevent cooling of said cold zone (10) and said support element (11) from causing trapping/immobilization of said analytes in said upstream (19) and downstream (21) portions.

26. Thermal modulator according to one or more of the preceding claims, characterized in that said electrically conductive elements (70, 71) are connected to current generating means for heating substantially continuously portions of said capillary (4) which are external with respect to said support element (11) and upstream (19) and downstream (21) with respect to said trapping portion (17) of said analysis capillary (4) which passes through the support element (11) and/or contacts said support element, in order to maintain said portions at a temperature higher than that of a thermostatic chamber (48) of said gas chromatograph (49) to which said thermal modulator is intended to be connected or in which said thermal modulator is intended to be housed.

27. Thermal modulator according to one or more of the preceding claims, characterized in that said current for substantially continuous heating is a constant current of about 0.1A-3A and/or an alternating current with a frequency greater than about 5Hz, preferably greater than about 100 Hz.

28. The thermal modulator according to one or more of the preceding claims, characterized in that said control means (14) are configured in such a way as to interrupt the transmission of said electric current to said conductive elements (70, 71) for substantially continuous heating when activating a pulsed electric current sent to said conductive elements (70, 71) for heating said trapping portion (17) to cause the release/desorption of the immobilized analyte in the trapping portion (17) itself, and vice versa.

29. The thermal modulator according to one or more of the preceding claims, characterized in that said heating means (80) are used to heat a section (81) of the analysis capillary (4) located outside the support element (11) and upstream of the trapping portion (17) of the analysis capillary that crosses and/or is in contact with the support element (11), said heating means being configured to send a current pulse to said section (81).

30. The thermal modulator according to one or more of the preceding claims, characterized in that said heating means (80) are intended to heat a section (81) of said analysis capillary (4) located outside said support element (11) and upstream of said trapping portion (17) of said analysis capillary which crosses and/or is in contact with said support element (11), said heating means comprising a first electrical contact (85) intended to input a pulsed current which causes heating of the section (81) and a second electrical contact (86) intended to output said pulsed current, and vice versa.

31. Thermal modulator according to one or more of the preceding claims, characterized in that said heating means (80) are intended to heat a section (81) of said analysis capillary (4) located outside said support element (11) and upstream of said trapping portion (17) of said analysis capillary which crosses and/or is in contact with said support element (11), said heating means comprising a configuration (100) in which the same analysis capillary (4) is folded so as to define at least one winding (83), said first electrical contact (85) being associated with said winding for inputting a pulsed current which causes the heating of said winding (83), said second electrical contact (86) being intended to output said pulsed current, and vice versa.

32. The thermal modulator according to one or more of the preceding claims, characterized in that said analytical capillary (4) is wound so as to define a helical path having at least one winding.

33. The thermal modulator according to one or more of the preceding claims, characterized in that said first electrical contact (85) and said second electrical contact (86) are associated with each winding at a position diametrically opposite each other.

34. Thermal modulator according to one or more of the preceding claims, characterized in that said heating means (80) are intended to heat a section (81) located outside said support element (11) and upstream of said trapping portion (17) of said analysis capillary which crosses and/or is in contact with said support element (11), said heating means comprising a configuration (100) in which the same analysis capillary (4) defines a substantially rectilinear segment with which said first electrical contact (85) and said second electrical contact (86) are associated for inputting a pulsed current which causes heating of said substantially rectilinear segment (83), said second electrical contact being intended to output said pulsed current, and vice versa.

35. The thermal modulator according to one or more of the preceding claims, characterized in that said control means (14) are also connected to said heating means (80) for causing heating of a section (81) of said analysis capillary (4) and are configured to selectively control the sending of a pulsed current to said first electrical contact (85).

36. Thermal modulator according to one or more of the preceding claims, characterized in that said pulsed current is sent to a first electrical contact (85) of said heating means, said section (81) of said analysis capillary (4) comprising pulses of substantially square wave having a substantially constant intensity and an effective duration of about 0.1 ms-10 ms.

37. Thermal modulator according to one or more of the preceding claims, characterized in that said control means (14) are configured so as to send said pulse current to said conductive elements (70, 71) to heat said trapping portion (17) to cause the release/desorption of the immobilized analyte in said trapping portion itself, at the same time or slightly delayed with respect to the first electrical contact (85) sending said current pulse to said heating means (80) for locally heating the section (81) of said analysis capillary (4).

38. Thermal modulator according to one or more of the preceding claims, characterized in that said heating means (80) are intended to heat a section (81) of said analysis capillary (4) located outside said support element (11) and upstream of said trapping portion (17) of said analysis capillary which crosses and/or is in contact with said support element (11), said heating means (80) comprising a configuration (101) in which said first conductive element (70) is associated with said analysis capillary (4) at a contact region (74) of said analysis capillary which is spaced apart from said entrance/origin of said trapping portion which crosses and/or is in contact with said support element (11), said first conductive element being provided for sending an electric current to said trapping portion (17) of said analysis capillary (4) suitable to cause an analysis for immobilization in said trapping portion (17) Heating of the release/desorption of the substance.

39. Thermal modulator according to one or more of the preceding claims, characterized in that the section (81) between the contact area (74) and the entrance/origin of the trapping part (17) of the analysis capillary crossing and/or in contact with the support element (11) is greater than the length of the trapping part (17) of the analysis capillary passing through and/or in contact with the support element (11).

40. Thermal modulator according to one or more of the preceding claims, characterized in that said pulsed current is sent to said first conductive element (70) for locally heating said section (81) of said analysis capillary (4), said pulsed current comprising current pulses of a substantially square wave having a substantially constant intensity and having an active duration of about 0.1 ms-10 ms.

41. The thermal modulator according to one or more of the preceding claims, characterized in that said control means (14) are configured so as to send a pulsed current to the first conductive elements (70, 71) for heating said trapping portion (17) to cause the release/desorption of the immobilized analyte therein, simultaneously or slightly delayed with respect to the sending of said current pulse provided for locally heating said section (81) of said analysis capillary (4).

42. Thermal modulator according to one or more of the preceding claims, characterized in that it comprises a housing structure (50) configured to connect said cooling system (8) with said thermostatic chamber (48) of a gas chromatograph (49).

43. The thermal modulator according to one or more of the preceding claims, characterized in that said casing structure (50) comprises:

-a lower part (51) intended to enter the thermostatic chamber of the gas chromatograph and to intersect with the analysis capillary (4),

-a central portion (52) in which a chamber is defined in said central portion (52), in which the cold zone (10) of the cooling system (8), the support element (11) supporting the analysis capillary (4) and the conductive element (70, 71) are housed.

44. The thermal modulator according to one or more of the preceding claims, characterized in that said central portion (52) comprises:

-a first half-shell (55) in which the cold area (10) is housed, said first half-shell being suitably filled with an insulating material (69),

-a second half-shell (56) filled with an insulating material (57) and in which said support element (11) is housed.

45. Thermal modulator according to one or more of the preceding claims, characterized in that said housing structure (50) is configured so that said central portion (52) is arranged externally, even very close, with respect to said thermostatic chamber (48) of said gas chromatograph (49) to which it is intended to be connected or in which it is intended to be housed.

46. Gas chromatograph (49) comprising a thermostatic chamber (48) and two gas chromatographic columns (1, 3) having different separation properties, characterized in that it comprises a thermal modulator (2) according to one or more of the preceding claims and interposed between said two gas chromatographic columns (1, 3).

Technical Field

The present invention relates to an improved thermal modulator for gas chromatography.

Background

Modulators are known for maximizing the efficiency of the separation process in conventional gas chromatographs for re-aggregating the sample bands and in two-dimensional gas chromatographs or GC x GC (integrated GC x GC) for preventing the distillate from leaving the first chromatographic column and subsequently separating it into fractions which enter at regular time intervals in the second chromatographic column, which usually, but not exclusively, has different separation properties from the first chromatographic column.

Gas chromatography is widely used in separation and analysis techniques in various fields, such as environmental fields, petrochemical fields, pharmaceutical fields, and even in one of flavors and fragrances.

Traditionally, gas chromatography systems consist of a gas chromatograph which mainly comprises an injector for introducing the sample to be analyzed, an oven or in any case a heater element, and different types of analog or digital detectors capable of recording traces of distillate and separated substances by means of electrical signals. The separation was performed by gas chromatography in a capillary chromatography column placed in a gas chromatograph oven and connected to a syringe and a subsequent detector. Inside it, as mentioned, a mixture of substances is made to flow by a carrier gas and separated by each interacting in a different way with the stationary phase of the chromatography column. The stationary phase consists of a layer of material, usually a polymer, which covers the inner walls of the capillaries that make up the column.

Despite great progress from the point of view of instruments and finding new stationary phases capable of separating the functional groups of key compounds, conventional gas chromatography methods are not sufficient for the complete analytical decomposition of so-called complex mixtures (samples containing hundreds of substances to be separated) nor even simpler from the point of view of the quantity of components but possessing non-resolvable samples with functional groups of concentrated analytical interest. For this reason, a technique known in the literature as GC x GC or two-dimensional gas chromatography has been developed, particularly in the last decade, which uses two gas chromatography systems connected together by a modulator.

In a preferred embodiment, the first system uses a syringe, a conventionally sized column (typically with an internal diameter of 0.25 mm-0.32 mm and a length of 30 m), while the second system uses a column that is extremely fast in separation process (e.g. variable length between 70cm and 2m with an internal diameter from 0.1mm to 0.2mm) compared to the first system, which is then connected to its output with a detector.

The two chromatography columns are placed in the same or different ovens and are connected to each other by a modulator, which is the object of the present invention, and which allows the output of a first chromatography column to be connected in series to the input of a second chromatography column. Essentially, the modulator plays a basic role in that it prevents the eluent compounds from flowing out of the first chromatographic column and reintroduces these small aliquots (aliquots) of eluent compounds in a rhythmic manner in the second chromatographic column to be separated by applying different separation principles to create the second chromatographic dimension. In this way, molecules that are not completely decomposed in the first dimension are completely decomposed in the second dimension and thus can be identified by the analyst.

In recent years, different modulators have been proposed and developed, but the most optimized and performance optimized type of modulator is one with thermal effects. In particular, the first thermal effect modulator involves the use of a local and floating heating element. Due to their low efficiency and complexity, they have been replaced by thermal modulators that are cooled by controlling the flushing of a gas that is intensively cooled by a cryogenic fluid (such as CO2 or nitrogen).

At present, thermal modulators with cryogenic liquid nitrogen cooling appear to be the best equipment available for two-dimensional gas chromatography modulation in terms of the range of molecules that can be separated (both super-and semi-volatile) and in terms of separation capacity (width of the second-dimensional chromatographic band).

In this modulator, a small portion of the gas chromatography column is frozen by a gas jet pre-cooled with liquid nitrogen, thereby immobilizing the analyte by condensing it on its inner walls. The analyte is then remobilized by a jet of hot gas (typically nitrogen) at an adjustable temperature, typically 250-400 ℃, for an adjustable time, typically 100-1000 ms. The cold and hot air flows are related to each other and cannot be modulated, since they come from the same pneumatic circuit at constant pressure.

Laboratory tests have shown that such a modulator has a high efficiency with a peak chromatogram resulting from the second chromatography column and a width at the base of up to 200 ms.

However, the mass of cooling gas (typically nitrogen) used is much higher than the size of the capillary to be cooled, and therefore most of its cooling capacity is not used to cool the capillary, but rather is spread in the gas chromatograph oven. Furthermore, such cold air flows disrupt the temperature regulation in the gas chromatograph oven, making it difficult to reach and stabilize the oven temperature set point. In essence, the cold air interferes with the oven temperature sensor, greatly changing the thermal state of the oven.

Therefore, using this type of modulator has the following disadvantages:

liquid nitrogen is produced in factories remote from the analysis laboratory by cooling with large industrial insulation, and is enclosed under pressure in large dewars, which are particularly difficult to handle and transport,

during transportation, part of the nitrogen becomes gaseous, thereby increasing the pressure in the dewar and further dispersing in the atmosphere through the control valve,

once it arrives at the laboratory, the nitrogen must be used continuously, otherwise it will be dispersed in the environment,

as mentioned previously, during the application for cooling the modulator, only a portion of the cold gas effective cooling capacity is used for cryoconcentration processing (cryofocalize) of the analyte, while most are dispersed in the oven.

In essence, in addition to being inefficient, cryogenic cooling by convection with the aid of cooled nitrogen is particularly expensive.

Furthermore, in cryogenic cooling using liquid nitrogen, the lowest temperature of the trapped/immobilized analyte corresponds to the lowest achievable temperature of liquid nitrogen (i.e. approximately-196 ℃), but in practice the temperature reached at the trapping/immobilization zone (also referred to as "trap") is much higher because of the heat absorbed by the nitrogen gas during its travel.

Alternatively, modulators are available on the market, which allow the use of cheaper cryogenic gases (e.g. CO)₂) (ii) a However, these modulators do not address the management and transportation issues associated with gas containment vessels; furthermore, these modulators are not suitable for conditioning of super volatile molecules, since they do not allow reaching low cryogenic temperatures as in the case of nitrogen.

Again, instead of a thermal modulator, fluid-type modulators have been proposed. In particular, these modulators require high column flow rates unless high split inputs are used, which are incompatible with mass spectrometers (one of the most commonly used detectors in this application), and in any case they require a large gas consumption. Moreover, the performance is less than what can be achieved with a thermal modulator in terms of the separation efficiency of the second column (for example, with these modulators obtaining chromatographic peaks with widths of about 750 ms-1000 ms, whereas the chromatographic peaks achieved with a thermal modulator are much narrower, i.e. with widths of about 200 ms).

Furthermore, in the modulator, in addition to the lowest achievable temperature, another key parameter is the speed at which this temperature is reached. In fact, in the thermal modulator, the analyte is concentrated and then blocked by coagulation or freezing inside the capillary connecting the first and second chromatography columns. It is necessary to activate the heater for a short time (several hundred milliseconds) and then allow the analyte to move again. However, when the heater is deactivated again, the temperature of the capillary must be restored to the initial state before activation of the heater as quickly as possible to again allow for a transient freezing action, thus allowing analyte to subsequently be blocked in the capillary.

In particular, in currently known modulators, the speed for capturing and releasing the analyte is not high enough. In more detail, the low speed of trap opening/closing is actually dependent on the type of solution used for gas convection (both for heating and cooling). In modulators with single-stage traps, sample leakage occurs through the trap itself due to the long time interval required to close (by cooling) the trap itself again after the trap has been released/opened (by heating); furthermore, the long time interval required to open the trap and the slow increase in the temperature of the trap itself lead to the expansion and differentiation of the peak bands ("peak bands"). In modulators with two-stage traps, the alternating activation/opening of the two-stage traps reduces the leakage problem, but the pressure pulse generated when the opening occurs in the first stage can interfere with the second chromatographic phase and the flow rate to the detector, resulting in the end result of significant changes in the detector signal.

Furthermore, the currently known modulators have the following drawbacks:

-the temperature of the capture/immobilization of the analyte is not readily determined and modified; in practice, usually, the trapping/immobilizing temperature is set to a value slightly higher than the temperature of the transition state of the cryogenic fluid (liquid/gas),

-the temperature of the analyte release is not easily determined and modified,

the temperature actually reached by the convective gas (and the capillaries) in both the cooling phase and the heating phase is difficult to detect and evaluate.

US2011/088452 describes a thermal micro-modulator in which a cooling device acts on a support frame and on a series of connection sections crossed by an analysis capillary. In US2011/088452, all heaters provided in the fine modulators function inside the support frame or inside said connection portion in contact with the cooling device.

WO2017/173447 describes a thermal modulator in which a capillary tube passes through a thermal buffer and a heat exchange block associated with a cold zone, which in turn is in contact with a cooling device. In WO2017/173447, all heaters are located inside a trapping part defined by a capillary portion passing through a heat buffer and a heat exchange block associated with a cold zone.

Disclosure of Invention

It is an object of the present invention to propose an improved thermal modulator for gas chromatography which overcomes the drawbacks of the conventional solutions.

It is another object of the invention to propose a modulator in which the range of capture/immobilization temperatures of the analyte is particularly wide.

It is a further object of the invention to propose a modulator in which the temperature range for releasing the analyte is particularly wide.

It is a further object of the invention to propose a modulator in which the rate of release and/or capture/immobilization of the analyte is particularly high.

It is another object of the invention to propose a modulator allowing a high spectral resolution.

Another object of the invention is to propose a modulator which produces peaks of particularly limited width and particularly high height at the output, thus improving the sensitivity of the detection system.

It is a further object of the invention to propose a modulator in which the range of modulation frequencies is particularly high.

Another object of the present invention is to provide a modulator that can be obtained in a simple, fast manner and at low production costs.

It is a further object of the invention to propose a modulator in which the thermal modulation is particularly efficient.

Another object of the invention is to propose a modulator which allows to increase the useful life of the capillary tube provided in the modulator itself.

It is a further object of the invention to propose a modulator which exhibits a particularly efficient cooling from an energy point of view.

It is another object of the invention to provide a modulator that is simple and inexpensive to use.

It is a further object of the invention to propose a modulator having alternative and/or improved characteristics with respect to the conventional modulators both in terms of construction and function.

It is another object of the present invention to provide a modulator that can be mass produced and used with substantially all gas chromatographs, both for one-dimensional gas chromatography applications and for two-dimensional gas chromatography applications, including those combined with low and high acquisition frequency mass spectrometers.

All these objects, both individually and in any combination thereof, as well as others that will be apparent from the following description, are achieved according to the invention with an improved modulator having the features set forth in claim 1.

Drawings

The invention is further elucidated with reference to the drawings, in which:

fig. 1 shows a gas chromatograph with an improved thermal modulator according to the invention in a vertical cross-sectional view;

FIG. 2 shows an enlarged detail of FIG. 2;

fig. 3 shows the internal elements of the modulator in a perspective view;

FIG. 4 shows the internal unit of FIG. 3 in an exploded perspective view;

FIG. 5 illustrates in perspective a different embodiment of the internal unit of FIG. 3;

FIG. 6 illustrates in perspective components of the internal unit of FIG. 3; and

fig. 7 shows an enlarged detail of a different embodiment of the internal unit of the modulator in a perspective view.

Detailed Description

As can be seen from the figure, the modulator 2 according to the invention comprises an analytical capillary 4, said analytical capillary 4 being intended to be connected between two gas chromatography columns 1, 3, said two gas chromatography columns preferably having different separation properties.

Conveniently, the analytical capillary 4 may be physically constituted by a separate section of the chromatography column with respect to the two chromatography columns 1 and 3, or alternatively it may be constituted by an end portion of the first chromatography column 1 or by an initial section of the second chromatography column 3.

Suitably, the analytical capillary 4 is made of a metal, preferably a nickel alloy (e.g. Inconel 600, Inconel625 or others) or of steel (e.g. SS316 and others).

Advantageously, the inner wall of the analytical capillary 4 is suitably inert from a chemical point of view. Advantageously, the inner diameter of the analytical capillary 4 is about 50 μm-250 μm, preferably 100 μm.

Advantageously, the wall thickness of the analytical capillary 4 is from 50 μm to 200 μm, preferably 75 μm.

The modulator 2 also comprises a cooling system 8, preferably consisting of a stirling cooler 8, which is a device that implements and uses a reverse stirling cycle. Alternatively, however, the cooling system may be a peltier unit (possibly also in series) or comprise other conventional cooling means.

The cooling system 8 comprises a cold zone 10 associated with the element 11, defining a cold group 12, which cold group 12 is in contact with a portion 17 of the analytical capillary 4, so as to cause cooling by conduction through the analytical capillary. In particular, the portion of the analysis capillary 4 is a portion in which the analyte is trapped/immobilized on the inner wall of the portion itself after reaching a certain particularly low temperature (also referred to as "trapping temperature"), and therefore the portion is hereinafter referred to as "trapping portion". Preferably, the trapping part 17 comprises a part of the analysis capillary 4 that is substantially in contact with the cold set 12 and is cooled by conduction from the cold set 12.

In particular, the element 11 is fixed to the cold zone 10 of the cooling system 8 so that said element 11 has substantially the same temperature as said cold zone 10. Advantageously, this is achieved by a planar coupling between the surface of the element 11 and the surface of the cold zone 10, preferably assisted by the interposition of a layer 15 of paste allowing heat conduction. Furthermore, this is achieved by the presence of an insulating material (insulating material for the cold zone 10 is indicated with 69 and insulating material for the elements 11 is indicated with 57) substantially around the entire cold group 12, so that the heat absorption of the entire cold group 12 is as small as possible, thus allowing the cooling system 8 to operate efficiently and thus reach the minimum operating temperature.

Conveniently, the element 11 is made of a material having a high thermal conductivity and being electrically insulating at least at its surface. In particular, the element 11 may have a substantially pyramidal shape or other suitable shape, also disc-shaped.

Conveniently, the element 11 comprises a seat 13, in which seat 13 the trapping part 17 of the analysis capillary 4 is preferably housed, the seat 13 preferably being constituted by a through cavity (preferably cylindrical) formed in the body of the element 11, or alternatively by a surface groove.

Conveniently, the portion of the analysis capillary 4 in contact with the element 11 and/or passing through the element 11 defines the trapping portion 17 and, in particular, in this portion, immobilises the analyte leaving the first chromatography column 1 by reaching the cryogenic temperature generated by the cold zone 10 of the cooling system 8.

Conveniently, the analytical capillary 4 is constrained/locked to the element 11 by means of a clamping device 60. Preferably, these clamping means 60 comprise a body 62 constrained to the element 11 by conventional fastening means 63 (for example screws) to keep the portion 17 of the analysis capillary 4 in contact with said element.

Advantageously, the element 11 has such a geometry as to define a mechanical interface and an optimal heat exchange between the cold zone 10 of the cooling system and the portion 17 of the analytical capillary 4.

Advantageously, the configuration of the element 11 is adapted to support the analytical capillary 4 to fix and maintain the trapping part 17 in contact with the cold group 12, so that it is at substantially the same temperature as the cold zone 10.

Advantageously, the element 11 is made of a metallic material having excellent thermal conductivity, but suitably electrically isolated at least on the surface. Preferably, the element 11 is made of, for example, aluminium or copper or alloys thereof with suitable surface insulation. Advantageously, the electrical insulation is obtained by surface treatment (anodization) or by applying an insulating film with good thermal conductivity.

As described above, the analysis capillary 4 includes: a catching portion 17, which catching portion 17 is preferably completely housed in the seat 13 of the element 11 and crosses/contacts the seat 13 of the element 11; and two portions 19 and 21, said two portions 19 and 21 being external to the seat 13 of the element 11 and respectively upstream and downstream of said portion 17. Preferably, the portion 17 defines a so-called "trap portion of the analysis capillary", while the upstream portion 19 defines a so-called "inlet portion", and finally, the portion 21 situated downstream defines a so-called "outlet portion". In other words, the portions 19 and/or 21 of the analysis capillary 4 are external to the support element 11 (and therefore not in contact with the support element 11) and are respectively upstream and downstream of the portion 17 of the analysis capillary 4 passing through and/or in contact with said support element 11.

Preferably, the trapping portion 17 of the analysis capillary 4 (i.e. the portion housed inside the seat 13 of the element 11) has a substantially rectilinear development, whereas the inlet portion 19 and the outlet portion 21 of said analysis capillary 4 initially have a substantially curved development and then continue to have a substantially rectilinear development.

The modulator 2 further comprises conductive elements 70, 71 associated with the analysis capillary 4 and connected to a power supply to deliver an electric current to said analysis capillary 4, so as to cause heating of the capillary section defining the trapping portion 17, and in particular for heating said portion 17 from a cryogenic temperature to a higher temperature (substantially corresponding to the boiling point of the analyte to be analyzed), so as to cause desorption of the analyte, whereby the analyte is released to leave the trapping portion 17 and move towards the inlet of the second chromatographic column 3.

Conveniently, the cold zone 10 of the cooling system 8 cools the element 11 when said portion 17 does not receive current from the conductive elements 70, 71, and then also cools the portion 17 of the analytical capillary 4 by conduction. Alternatively, when portion 17 receives a particularly high pulse current from conductive elements 70, 71; the heating action of said portion 17 is so rapid and adiabatic (i.e. it does not emit heat to the outside) as to exceed the above-mentioned cooling.

The transmission of the current to the conductive elements 70, 71 is managed by a control unit (not shown) of the modulator 2, said modulator 2 suitably controlling their activation and deactivation by sending a pulsed current (preferably substantially square-wave current pulses) generated by a suitable electronic system, preferably by charging and discharging capacitors. Preferably, the pulsed current sent to the conductive elements 70, 71 is about 10A-200A, preferably about 80A. Suitably, the effective duration of the pulse current modulation is from 0.1ms to 10ms, preferably 0.5 ms; suitably, the frequency of the pulsed current is about 0.03 Hz-10 Hz, preferably about 0.1 Hz-1 Hz.

Conveniently, these current pulses are sent to the input and returned to the output by means of a suitable conducting element 7 (preferably a cable or copper tube) associated with the conducting elements 70, 71 by means of stable (preferably mechanical) constraints.

In particular, the conductive elements comprise at least a first conductive element 70 for input (or output) of current and at least a second conductive element 71 for output (or input) of current.

Preferably, the heating means are defined by the same portion of analysis capillary 4 made of electrically conductive material interposed between said at least one first electrically conductive element 70 and said at least one second electrically conductive element 71.

Preferably, said first and second conductive elements 70 and 71 are respectively associated, by micro-welding, with the inlet section 72 and the outlet section 73, respectively, of the portion 17 of the analysis capillary 4 passing through the seat 13 of the element 11. In more detail, at least one first conductive element 70 is directly associated with the inlet section 72 of the portion 17 of the analysis capillary 4, in correspondence with a contact zone 74, whereas at least one second conductive element 70 is directly associated with the outlet section 73 of the portion 17 of the analysis capillary 4, in correspondence with a contact zone 79.

Conveniently, the inlet section 72 and the outlet section 73 correspond respectively to the inlet end and to the outlet end of the analysis capillary 4 inside the element 11, or are two portions placed respectively upstream and downstream of said starting and outlet ends, although outside the trapping portion 17.

Advantageously, as shown in fig. 5, two first conductive elements 70 may be provided, which two first conductive elements 70 are associated with the inlet section 72 of the analysis capillary 4, corresponding to two respective contact areas 74. Correspondingly, two second electrically conductive elements 71 may be provided, which two second electrically conductive elements 71 are associated with the outlet section 73 of the analysis capillary 4, respectively, corresponding to two respective contact regions 79.

Conveniently, the conductive element 7 is in contact with the conductive elements 70 and 71 to allow current to flow from the first conductive element 7 to the second conductive element. In particular, for this purpose, constraining means 75 are provided for constraining the conductive elements 70, 71 to the conductive element 7 and preferably both to the element 11.

Advantageously, these constraining means 75 comprise at least two plates 76, each plate 76 being pressed onto the element 11 by conventional fixing means 77 (for example screws) so that the conductive element 70 or 71 and the respective conductive element 7 between the conductive element 70 or 71 and the corresponding plate 76 are blocked and kept in mutual contact. Conveniently, the conductive element 7 may be incorporated in the plate 76 such that, once the plate is secured to the element 11, surface portions of the conductive element 7 are in contact with the conductive elements 70 and 71. Preferably, the conductive element 7 is received in a corresponding surface slot 78 formed on the surface of the plate 76.

Preferably, the conductive members 70 and 71 are made of a metal material. Advantageously, the conductive elements 70 and 71 are filiform and preferably consist of metal capillaries of the same type as the analysis capillary 4. Advantageously, the conductive elements 70 and 71 comprise capillaries made of metal, preferably of nickel alloy (such as Inconel 600, Inconel625 or others) or steel (such as SS316 and others). Advantageously, the inner diameter of the capillary is from about 50 μm to about 250 μm, preferably about 100 μm. Advantageously, the wall thickness of the capillary is from about 50 μm to about 200 μm, preferably about 75 μm.

Preferably, the electrically conductive elements 70 and 71 are micro-welded on the at least one inlet section 72 and the at least one outlet section 73 with respect to the trapping part 17 of the analysis capillary 4. Advantageously, the conductive elements 70 and 71 contact the analysis capillary 4 at the beginning of the trapping portion 17 of the analysis capillary 4 (i.e. the inlet end of the capillary 4 in the element 11) and at the terminating end (i.e. the outlet end of the capillary 4 from the element 11).

Conveniently, the current pulse arriving from the inlet conductive element 7 passes through the first conductive element 70 and from there reaches the trapping part 17 of the analysis capillary 4, causing the heating of said trapping part 17 and therefore of the condensed compounds and/or gases contained therein; subsequently, after passing through the trap portion 17 of the analytical capillary 4, the current flows to the outlet conductive element 71 and from there to the grounded outlet conductive element 7. Conveniently, the current path may also be in the opposite direction, then entering the portion 17 of the analysis capillary 4 through the second conductive element 71 and exiting from the portion 17 through the first conductive element 70.

Advantageously, the control unit is also configured to send an electric current to the conductive elements 70 and 71, which causes a substantially continuous (i.e. stable in time) heating of the portions 19 and/or 21 of the analysis capillary 4 that are external to the support element 11 and respectively upstream and downstream of the portion 17 of the analysis capillary 4 that passes through and is in contact with said support element. Basically, the control unit is also configured to send an electric current to the conductive elements 70 and 71a, which causes a substantially continuous heating (i.e. stable in time) of the inlet portion 19 and/or the outlet portion 21 and possibly also the trapping portion 17 of the analysis capillary 4.

Conveniently, the current sent to the conductive elements 70 and 71 in order to cause the above-mentioned continuous heating is a particularly low direct current (for example, about 0.1A-3A, preferably 1A, for each branch) or an alternating current with a frequency greater than about 5Hz, preferably greater than about 10Hz, even more preferably greater than about 100 Hz. Conveniently, this current, apt to cause a substantially continuous heating, is transmitted to the conductive elements 70 and 71 and, at the contact areas 74, 79 of the conductive elements 70 and 71 with the analysis capillary 4, to the inlet portion 19 and to the outlet portion 21 of the analysis capillary 4 and possibly also to the trapping portion 17. Conveniently, this current sent to the conductive elements 70 and 71 and capable of causing a substantially continuous heating is a current for maintaining the temperature of the inlet portion 19 and the outlet portion 21 higher (hotter) than the cryogenic fixing temperature provided in the trapping portion 17, preferably maintaining the temperature of said portions at a temperature not lower than that of the thermostatic chamber of the gas chromatograph.

Conveniently, two corresponding electrical connections 97 are provided at the inlet portion 19 and the outlet portion 21 for outputting the current flowing through said portions. Preferably, these electrical connections 97 are located inside the thermostatic chamber 48 of the gas chromatograph 49.

Suitably, therefore, an electric current capable of causing a substantially continuous heating is sent both to the first conductive element 70 and to the second conductive element 71, and the electric current reaches the inlet portion 19 and the outlet portion 21 respectively through the respective contact areas 74, 79 of these means in contact with the inlet section 72 and the outlet section 73 of the analysis capillary 4. Suitably, the electric current thus sent passes through said portions 19 and 21 of the analytical capillary 4 and then exits through respective electric connections.

Advantageously, the electric current sent into the inlet portion 19 and the outlet portion 21, capable of causing a substantially continuous heating, allows to suitably control/regulate the temperature in said portions, so as to prevent the cold group 12 from excessively cooling these portions 19 and 21, thus also causing, for example, the analyte to be trapped/immobilized in a zone external with respect to the portion 17. In this way, the analyte is allowed to pass through the analysis capillary 4 appropriately, avoiding the immobilization/aggregation of the same analyte before reaching the portion 17 or the re-aggregation/remobilization again after passing through the portion 17 (i.e. during the heating/desorption cycle and after being released by the heating/desorption cycle).

Advantageously, the transmission of an electric current to the trapping part 17, apt to cause a substantially continuous heating of the trapping part, by means of the conductive elements 70 and 71, allows to adjust and vary the trapping temperature defined by the cold zone 10, and this ultimately improves the concentration and the position of the analytes.

Advantageously, the control unit is configured to control the electronic system and/or the generator so that the transmission of the electric current adapted to cause a substantially continuous heating to said conductive elements 70 and 71 is interrupted when the transmission of a pulsed electric current to the conductive elements 70 or 71 is activated to heat the capture portion 17 to cause the release/desorption of the immobilised analyte in the capture portion, and vice versa.

Advantageously, the modulator 2 also comprises heating means 80 for causing heating of the section 81 of the analysis capillary 4, preferably locally and substantially instantaneously heating the section 81 of the analysis capillary 4 and therefore the gas present in this section, to cause expansion of said gas along said capillary. In particular, considering that the capillary has a constant cross section, the gas contained in the heated capillary section 4 expands along the longitudinal development of the capillary itself.

Conveniently, said section 81, which is heated, is defined outside and upstream of the portion 17 of the capillary tube that passes through and/or is in contact with the support element 11 (i.e. the trapping portion 17), so that the expansion of the gas causes a thrust effect directed towards said portion 17.

Conveniently, the heating of the section 81 located outside and upstream of the trapping portion 17 is obtained by sending a current pulse to said section.

Advantageously, in the first embodiment, said heating means 80 for heating the section 81 of the analysis capillary defined upstream of the trapping section 17 comprise a first configuration 100 in which the same analysis capillary 4 has a folded portion 82 to define one or more windings 83, each winding 83 defining a closed shape with two opposite sections 84 facing each other.

Preferably, each winding 83 substantially defines the circumferential path of the capillary itself. Preferably, the analytical capillary 4 is wound to define a helical path of at least one turn. Conveniently, at the opposite section 84 of each winding 83 of the analysis capillary 4, a first electrical contact 85 and a second electrical contact 86 are applied, respectively. In particular, a first electrical contact 85 is provided for sending an electric current to the capillary folded in this way, while a second electrical contact 86 is provided for grounding the sent current. Suitably, the current may also flow in the opposite direction, then enter the winding 83 of the analytical capillary 4 through the second electrical contact 86 and exit from the winding 83 itself through the first electrical contact 85. Preferably, the first electrical contact 85 and the second electrical contact 86 are applied in diametrically opposite positions along each winding 83 of the capillary 4. Suitably, the branches 87 of the capillary 4, interposed between the first and second electrical contacts 85, 86 and opposite each other, have substantially the same length, so as to balance the current passing through these branches.

Conveniently, in an embodiment not shown here, the section 81 may also be a rectilinear segment interposed and defined between the first 85 and second 86 electrical contacts.

Conveniently, said heating means 80 are managed by the control unit of the modulator 2, which suitably controls the activation and deactivation thereof by sending suitable current pulses generated by the electronic system, preferably by charging and discharging a capacitor. In particular, the control unit controls the transmission of a pulsed current (preferably a substantially square-wave current pulse) of substantially constant intensity (preferably equal to 10A-100A, preferably 50A) to the first electrical contact 85; in particular, suitably, the effective duration of these current pulses is greatly reduced, being about 0.1ms to 10ms, preferably 1 ms; suitably, the frequency of the pulsed current is about 0.03 Hz-10 Hz, preferably about 0.1 Hz-1 Hz.

Conveniently, the fact that the current sent to the section 81 of the analysis capillary 4 is particularly strong and of short duration allows avoiding the energy diffusion towards the outside and causing a local heating of said section, and in particular of the winding 83 of the capillary itself. In more detail, such heating of the section 81 of the analysis capillary 4 causes a corresponding increase in the temperature, and therefore in the volume, of the gas contained in the folded portion. In particular, considering the prevention of the expansion of the gas in the radial direction by the inner wall of the capillary, this expansion can be practically effected just along the longitudinal development of the capillary itself, thus causing a linear movement/progression of the gas upstream and downstream with respect to said folding and heating section.

Conveniently, in order to increase the linear movement/advancement of the gas caused by the heating means 80, it is possible to act on the number of windings 83 and on the geometry of these windings, as well as on the intensity and duration of the current pulse transmission.

Advantageously, the linear expansion of the gas causes a thrust of the analyte inside the trapping portion 17, thus facilitating the advancement of said gas towards the outlet portion 21 following the release/desorption caused by the heating of said portion 17 obtained by the current sent by the conductive element 70 or 71.

Advantageously, the control unit is configured so as to send a pulsed current to the conductive element 70 or 71, simultaneously or slightly delayed with respect to the current pulse sent to the first electrical contact 65 of said heating device 80, for heating the trapping portion 17 of the capillary 4, so as to cause the release/desorption of the immobilized analyte in said trapping portion, the first electrical contact 85 of said heating device 80 being used for locally heating the section 81, said heating device 80 expanding the gas towards the bottom of said section 81 to push and advance the released/desorbed analyte towards the outlet portion 21.

Advantageously, in the different embodiment shown in fig. 7, said heating means 80 for causing a localized heating corresponding to the section 81 of the analysis capillary defined upstream of the trapping portion 17 comprise a second configuration 101 in which said first conductive element 70 (i.e. the inlet conductive element) is associated with the upstream portion 19 of said analysis capillary 4, at a distance from the starting portion 89 with respect to said trapping portion 17 (i.e. the end with respect to the capillary 4 entering the element 11), corresponding to the section 81, preferably by micro-welding, said first conductive element 70 being provided for sending a pulsed current to the trapping portion 17 to heat it, so as to cause the release/desorption of the analyte immobilized in said trapping portion.

Conveniently, as shown in fig. 7, the section 81 between the contact zone 74 (where the conductive element 70 is in contact with the analysis capillary 4) and the starting point 89 of the trapping portion 17 (corresponding to the position where the capillary 4 enters the interior of the element 11) is much greater than the length of the trapping portion 17 (i.e. the section of capillary 4 inserted/housed in the element 11 and passing through the element 11 and thus in intimate contact with the cold pack 12).

Thus, in this way, in correspondence with the contact zone 74, a pulsed current is sent from the inlet conductive element 70 to the capillary 4 and thus causes, through the capture portion 17, desorption/release of the analyte found in said capture portion 17; however, in addition to this, the fact is that an electric current is sent to the capillary 4 before the trapping part 17 causes a local heating of the aforementioned section 81, thus generating an expansion of the gas along the longitudinal development of the capillary, thus pushing the released analyte away from the trapping part and towards the outlet part 21.

Basically, these heating means 80 are configured to cause a local heating (preferably by electrical heating) of a section 81 of the analysis capillary 4 arranged upstream of the trapping section 17, said heating means 80 expanding the gas contained in said section particularly rapidly. Suitably, this expansion causes a thrust of the analytes located inside the portion itself and which have been released after heating said portion, towards the exit of the trapping portion 17. In particular, this expansion of the analyte out of the capture portion 17 occurs before the analyte is immobilized again within the portion.

Conveniently, also in this second configuration 101, said heating means 80 are managed by the control unit of the modulator 2, which suitably controls its activation and deactivation by sending suitable current pulses generated by the electronic system, preferably by the charging and discharging of the capacitor. In particular, the control unit controls the transmission of a pulsed current (preferably a substantially square-wave current pulse) of substantially constant intensity (preferably equal to 10A-200A, preferably 80A) to the first conductive element 70; in particular, suitably, the effective duration of these current pulses is greatly reduced, being about 0.1ms to 10ms, preferably 0.5 ms; suitably, the frequency of the pulsed current is about 0.03 Hz-10 Hz, preferably about 0.1-1 Hz.

Conveniently, it should be understood that the same modulator 2 may comprise heating means 80 realized according to the first configuration 100 only (see fig. 1 and 2), or heating means 80 realized according to the second configuration 101 only (see fig. 8), or again it may comprise heating means 80 realized according to the first configuration 100 and the second configuration 101.

Advantageously, in configurations 100 and 101, these heating devices 80 cause a "pulsed" injection of analyte in the second dimension of the chromatography column.

Advantageously, these heating means 80 allow a very rapid injection into the second chromatographic column for the peak of the sample coming out of the trapping part 17 of the capillary 4 of the modulator 2, due to the rapid evaporation (release) of the sample in the trapping part 17. In this way, the peak of the samples at the output of the modulator is extremely narrow, and therefore, given a certain number of samples, the height of the peak is extremely high and the signal-to-noise ratio is significantly improved. This is particularly advantageous because very narrow peaks are ideal for detection at acquisition frequencies of up to 1000Hz or higher by fast detectors such as time-of-flight mass spectrometers and flame ionization detectors.

Furthermore, conveniently, these heating means 80, upstream with respect to the trapping section 17, do not contribute to the extension/widening of the second dimension band. In particular, the expansion volume determined by the heating means 80 is so small and the duration of such expansion is so short that they do not cause any extension/widening of the bands of the chromatography column. Advantageously, these heating means 80 may be suitably configured to obtain a desired thrust effect on the analyte; for example, to reduce the local temperature rise in section 81, the capillary bundle length affected by the rise may be increased and the amplitude of the injected current reduced.

Advantageously, the modulator 2 further comprises a housing structure 50, which housing structure 50 is configured so that the cooling system 8 is connected to the thermostatic chamber (oven) 48 of the gas chromatograph 49.

In particular, the shell structure 50 comprises:

-a lower part 51, preferably tubular, entering the thermostatic chamber of the gas chromatograph and traversed by the analysis capillary; advantageously, the lower portion 51 is suitably filled with an insulating material,

-a central portion 52, within said central portion 52, a chamber is defined, which houses the cold zone 10 of the cooling system 8, the element 11 supporting the analysis capillary 4 and the conductive elements 70 and 71,

-an upper portion 53, fixed to the main body of the cooling system 8.

In more detail, the chamber defined in the central portion 52 is delimited by:

-a first upper half-shell 55, in which the cold area 10 is housed, said cold area 10 being suitably filled with an insulating material 69,

-a second lower half-shell 56, suitably filled with an insulating material 57, and in which the element 11 is housed; preferably, the insulating material 57 is constituted by polyurethane foam, suitably injected inside said second lower half-shell.

Advantageously, the housing structure 50 is configured such that a central portion 52 is arranged externally (even in close proximity) with respect to the thermostatic chamber 48 of the gas chromatograph 49, said central portion 52 housing the cold zone 10, the element 11 and the analysis capillary 4 and the conductive elements 70 and 71. Advantageously, a through hole is formed in the wall 18 of the thermostatic chamber 48 of the gas chromatograph, inside which the lower part of the housing structure 50 is inserted. Suitably, outside the thermostatic chamber 48 of the gas chromatograph 49, a suitable support structure 59 is provided for the main body 22 of the cooling system 8.

Conveniently, in an alternative embodiment not shown, the cold zone 10 of the cooling system 8 (or at least the lower surface thereof), the element 11 and the unit comprising the analysis capillary 4 and the conductive elements 70 and 71 are all inserted and housed inside the thermostatic chamber (oven) 48 of the gas chromatograph 49.

In more detail, the gas chromatograph 49 may have a single thermostatic chamber 48, which thermostatic chamber 48 completely houses the two gas chromatography columns 1, 3 in addition to housing the above-mentioned components of the modulator 2. Alternatively, the gas chromatograph may comprise, in addition to the thermostatic chamber 48 housing the above-mentioned components of the modulator 2, a second thermostatic chamber (not shown) which is separate with respect to said first thermostatic chamber 48 and is traversed by the first gas chromatography column 1 or by the second gas chromatography column 3.

Furthermore, at the wall 18 of the thermostatic chamber 48 of the gas chromatograph and/or at the housing structure 50, further through holes are formed to allow the passage of cables. In particular, these holes are necessary to allow the passage of cables (not shown) which, by means of the electrical connection 97, connect the electronic system for generating electrical current with the conducting element 7 and with the heating device 80 for the local heating section 81.

Conveniently, the control unit is connected to a power supply (not shown) of the entire modulator 2.

Advantageously, the control unit is connected to an electronic system for charging and discharging a capacitor capable of storing a predetermined (settable) quantity of electric energy and then discharging it. In particular, the electronic system for charging and discharging through the capacitor is controlled by the control unit to generate, during the discharge phase, a pulsed current signal which passes through the conductive element 7 and the conductive element 70 or 71, so as to cause the trapping part 17 and the heating device 80 to heat up in order to locally heat the section 81.

Advantageously, the computer 40 is connected to a control unit on which is installed suitable software acting as an interface for programming and setting the entire modulator 2 and for displaying and processing the results.

The operation of the modulator 2 according to the invention is as follows. Once the cooling system 8 has been activated, it will start cooling until the cold zone 10 reaches a certain cryogenic temperature defined on the basis of the analyte to be analyzed. In particular, depending on the analyte to be analyzed, it is possible to reach particularly low cryogenic temperatures, down to-210 ℃. Once the cryogenic temperature is reached, the cooling system 8 (which preferably comprises a stirling cooler) is kept active at all times to keep it stable, or is controlled according to a predefined temperature rise profile when performing gas chromatographic analysis.

The conductive cooling of the analysis capillary 4 at the capture section 17 by means of the element 11 leads to the immobilization of the analyte through the capillary section at cryogenic temperatures.

The control unit then controls the sending of a suitable pulsed current signal which causes the activation of the conductive element 70 or 71 within a well-defined time interval between 0.1ms and 10ms, thus causing the temperature rise of the trapping part 17 of the capillary 4; in particular, in this way an increase in the temperature of the trap part 17 is obtained, i.e. the trap part 17 reaches a heating temperature (essentially corresponding to the boiling point of the analytes to be analyzed) from a cryogenic temperature, and this leads to desorption of the analytes, thereby releasing them rhythmically one after the other.

Usually, the above-mentioned current pulses obtained from capacitive discharge are generated starting from an initial discharge voltage, which has been previously set and reached during the charging phase, with a voltage value comprised between 10 volts and 100 volts. These discharges are between 0.1ms and 10ms in duration to enable immediate release of the cryo-immobilized analyte and avoid excessive temperature rise.

Once the sequence of current pulse discharges of the capacitor and therefore the heating of the trapping portion 17 by the conductive elements 70 and 71 is terminated, the temperature of said portion 17 rapidly returns to the cryogenic temperature due to the cooling by conduction by the cold group 12 working on said portion 17 of the capillary 4.

As mentioned, advantageously, the cooling system 8 allows rapid freezing/immobilization of the analyte to be analyzed at very low temperatures (down to-210 ℃) depending on the analyte to be analyzed, said cooling system 8 preferably comprising a stirling refrigerator 8. Furthermore, in order to prevent the analytes from being immobilized again (recrystallized) before leaving the trapping portion 17, the expansion of the gases and the thrust subsequently generated by the means 80 for locally heating the section 81 of the capillary 4 upstream of said trapping portion 17 favour their exit.

Advantageously, during the gas chromatographic analysis, the control unit can conveniently control the variation between the discharge potential and/or the modulation time (i.e. the time between the start of the discharge and the start of the next discharge) and/or the desorption time (also called "duty cycle", i.e. the fraction of the modulation time that sends the current to the conductive element associated with the analysis capillary) according to a preset slope, in order to optimize the performance of the analysis itself.

From the above it is evident that the modulator according to the invention has further advantages over conventional modulators:

the immobilization temperature of the analyte can vary within a particularly wide range and this is achieved by controlling the temperature of the cold zone of the cooling system (stirling reverse cycle refrigerator and/or peltier cell) with feedback,

the analyte release temperature can vary within a particularly wide range and this can be achieved by correspondingly controlling the duration and/or amplitude of the current sent to the heating means acting on the capillary tube,

the chromatographic resolution in the first and second dimensions is particularly high due to the direct hydrodynamic connection of the input and output of the modulator to the respective gas chromatography column,

-the rate of release of analyte is extremely high; this results from a very fast heating of the analyte-trapping part, in particular by analyzing the direct connection between the capillary and the capillary part defining the heating means and by sending a particularly high current to said part of the heated capillary in an extremely short period of time.

-the speed of immobilization of the analyte is very fast (i.e. approximately 1 ms-2 ms); this is obtained by a very rapid cooling, which comes from the fact that: the analytical capillary is in direct contact with the cold zone of the cooling system via the housing element.

Furthermore, the modulator according to the invention is particularly advantageous in the following respects:

-without the use of nitrogen or other gases,

no interference to the inner state of the inner chamber of the gas chromatograph,

-greater cooling capacity is obtained by using a reverse stirling cycle refrigerator, in partial cold contact with the analysis capillary tube through the interposition of a support element; in particular, it allows very low temperatures of about-210 ℃ to be reached, whereas traditional nitrogen cooling is not allowed to reach below-196 ℃; moreover, once heating is over, it allows a particularly rapid (substantially instantaneous) return to the trapping condition (i.e. from the heating temperature to the cryogenic temperature);

-allowing the cooling temperature to be set to different values substantially comprised in a temperature range between-210 ℃ and 30 ℃ according to the analysis needs;

-during gas chromatography it is possible to control and modify the modulation time, i.e. the time from the start of the discharge to the start of the next discharge, and the "duty cycle" of the modulation, i.e. the fraction of the modulation time that the current is sent to the conductive element,

particularly flexible, i.e. it can be used with essentially any type of detector.