IT201900008442A1 - Chemical analysis system using gas chromatography separation and spectrometry of sample mixtures - Google Patents

Description

Chemical analysis system using gas chromatography separation and spectrometry of sample mixtures

The present invention relates to the field of miniaturized systems for pre-concentration and chemical analysis through (gas-) chromatographic separation and spectrometry of sample mixtures.

State of the art

In general, various types of portable chemical analysis systems capable of identifying illicit or toxic substances in traces (sub-ppm concentrations) are known. However, these systems, in addition to having limitations, are bulky and therefore can only be used in the laboratory.

The only type of instrumentation currently capable of carrying out measurements of this type in the field is based on the coupling between gas chromatography columns (GC) and mass spectrometers (MS), as in the case of the Inficon Hapsite and the FLIR Griffin G510. However, the main flaws of these mass spectrometers are as follows:

1) require complex and expensive pumping systems to create a high vacuum inside the spectrometer;

2) have problems detecting substances with a molecular weight below 40, such as, for example, toxic gases such as ammonia and phosphine;

3) conventional GC columns used in such instruments are difficult to heat and slow to cool, lengthening the time between two consecutive analyzes.

On the other hand, as known, instruments based on the coupling between GC separation techniques and infrared absorption spectrum analysis techniques (IRAS = Infra Red Absorption Spectroscopy) have an identification capacity at least comparable and sometimes superior to GC-MS instruments. In particular, GC-IRAS is the most flexible and powerful laboratory method for the identification of drugs, designer drugs and their precursors [see the publication: "Recommended Methods for the Identification and Analysis of Amphetamine, Methamphetamine and their Ring-Substituted Analogues in Seized Materials ”(United Nations, 2006)]. In fact, unlike mass spectroscopy, infrared absorption spectroscopy allows to identify not only known illicit substances, but also similar substances, with the same functional groups but specially modified to not be recognizable ("designer drugs"). To date, however, there are no portable GC-IRAS instruments, since traditional IRAS analyzers (both dispersive and Fourier transform type) operate with analysis cells of significant volume, which cannot be coupled with miniaturized GC columns.

Added to this is the fact that the GC systems existing today also have limitations, which often affect the final measurement of the spectrometers.

In fact, purge & trap pre-concentration systems are known, used to increase the concentration of a sample before injecting it into a gas chromatography (GC) column for the separation and detection of the analytes contained therein. They too are implemented almost exclusively in laboratory measurement systems, and generally consist of tubes (metal or glass) filled with specific absorbent materials which, at room temperature or cooled, retain the molecules of interest (analytes) from the flow of sample. This sampling and preconcentration phase can also be long (tens of minutes), in order to absorb a large amount of sample. When enough sample has been collected, heating is generally applied to the tube (and therefore to the absorbent material contained) which releases the trapped molecules (thermal desorption) within a flow of carrier gas. An attempt is made to carry out this release in the shortest possible time, in order to release the molecules absorbed within a possibly reduced volume of carrier gas, thus increasing the concentration of the sample.

For example, a pre-concentrator samples 10 liters of air within a few minutes, and then releases the absorbed content within a volume of only 100 milliliters. The concentration factor is ideally 100x.

However, it is generally difficult to heat the pre-concentration tubes very quickly (it is a matter of bringing them up to 350 ° C in a few seconds): to heat conventional tubes it is necessary to dissipate a considerable electrical power.

In bench / laboratory GC systems, which today use purge & trap pre-concentration systems such as those described above, the injection circuit is generally made with mechanical valves of considerable size and complexity, which however can boast excellent characteristics of reliability and robustness. even at high temperatures ([1], see below).

On the other hand, there are MEMS (on-chip) injection systems for gas chromatography, also known as micro-gas chromatography (μGC), based on diaphragm valves in polymeric materials (generally Kapton) actuated by pressure (for example MEMS injectors [2] ). The advantage of these types of injector is that:

1) they implement an injection circuit with very low dead volume; And

2) they can be easily heated to temperatures up to over 200 ° C, an important feature to avoid the condensation of heavy / high-boiling molecules.

To the knowledge of the inventors, all GC MEMS injectors to date implement the injection of a sample loop and not of a pre-concentrator, i.e. they inject a known and controlled volume of gaseous sample, as it is taken directly from the environment to be analyzed. This means that the concentration of the injected molecules is equal to the concentration in the environment (and not greater, as in the case of the preconcentration illustrated above and made with a totally different technology).

One of the Applicants (IMM institute of the National Research Council) has developed in the past and published a miniaturized / portable "mini-GC" [3] system, based on preconcentration in a MEMS (therefore not in a glass or metal tube) , on injection into a MEMS GC column, and on a detector (which can be of different types). This system allows you to carry out the GC analysis of some low concentration samples through the pre-concentration phase. The advantages of this solution are: i. The pre-concentrator allows to analyze for example benzene up to concentrations of ppb fractions;

ii. The MEMS pre-concentrator can be heated very quickly, with ramps up to> 50 ° C / s, thus allowing a rapid pre-concentrated injection without the need for cryogenic traps, i.e. devices designed to focus the sample at the top of the GC column through rapid thermal cycles: capture of the sample at cryogenic temperature (generally with the aid of liquid nitrogen or expansion of compressed gas) and subsequent injection into the column through rapid heating.

The mini-GC system, which was developed as a highly application-specific device for the analysis of benzene in air, however, has the main disadvantage that the injection circuit is implemented using commercial miniature solenoid valves, characterized by:

to. significant internal dead volumes, which worsen the quality of the injection due to a dilution / diffusion of the sample, thus worsening the performance of the separation column; b. impossibility of being used at temperatures above 60 ° C, which in principle prevents the analysis of samples with boiling temperatures above this temperature (thus preventing many applications other than benzene).

In addition to the publication cited above, there are others about pre-concentration in the GC technique, which also use MEMS technology, for example [4] - [6], but which share similar disadvantages.

Patent application WO2017180933A1 uses a pre-concentrator and a separation column, but it is not easily miniaturized and the injection is done with conventional valves, so it is not possible to heat them to measure low volatile compounds, and also the dead volumes of the valves that they use are too high.

There remains therefore a need for a chemical analysis system capable of identifying illicit or toxic trace substances (sub-ppm concentrations) in a reliable and broad-spectrum manner, in particular but not exclusively, making use of compact and high-performance miniaturized GC systems. efficiency as well as economical and efficient spectrometric systems, for use in the field and beyond.

Purpose and object of the invention

The object of the present invention is to provide a chemical analysis system which uses a gas-chromatographic column and a spectrometer and which solves all or part of the problems of the prior art.

A further aim of the present invention is to provide a chemical analysis method for gas-chromatographic separation and spectroscopy that solves all or part of the problems of the prior art.

The subject of the present invention is a system and a method of chemical analysis for gas chromatographic separation and spectroscopy according to the attached claims.

Detailed description of examples of implementation of the invention

List of figures

The invention will now be described for illustrative but not limitative purposes, with particular reference to the drawings of the attached figures, in which: - Figure 1 shows a schematic representation

of the combined (gas-) chromatographic system e

photoacoustic according to an embodiment of the

present invention;

- figure 2 shows a lateral section of the cell

QEPAS photoacoustics according to one embodiment

of the present invention;

- figure 3 shows a vertical front section

of the same cell of Figure 1;

- figure 4 shows a horizontal section of the

same cell of Figures 2 and 3;

- figure 5 shows a side sectional diagram

of an embodiment of the GC device

according to the invention;

- figure 6 shows a side sectional diagram

simplified, with indication of flows, of

device of figure 1;

Figure 7 shows a three-dimensional view of

greater detail of the device of figures 5

and 6;

- figure 8 shows a functional diagram of

detail of the device according to figure 7, in

a first operational state of pre-concentration; - figure 9 shows a functional diagram of

detail of the device according to figure 7, in

a second operational state of GC analysis;

Figure 10 shows the flow directions in one

microvalve open (b) and closed (a) in one form

of realization of the device according to the invention;

- Figure 11 shows in (a) a chromatogram of the integral absorbance of the simulant of nerve agent dimethyl-methylphosphonate and simulant of methyl-salicylated vesicant agent in ethanol (a) and the IR spectra of the two compounds eluted at 80s (b) and 120s (c), in an experiment with an embodiment of the system of Figure 1; And

- figure 12 shows some IR spectra measured by an embodiment of the GC-QEPAS system of fig. 1: 10 ppm of 2-methoxy-ethanol (EGME) sampled for 60 s (a) and 2 ppm of dipropylene glycol methyl ether (DPGME) sampled for 120 s (b).

It is specified here that elements of different embodiments can be combined together to provide further unlimited embodiments while respecting the technical concept of the invention, as the average person skilled in the art understands without problems from what has been described.

The present description also refers to the known art for its implementation, with regard to the detailed characteristics not described, such as for example less important elements usually used in the prior art in solutions of the same type.

When an element is introduced, it always means that it can be “at least one” or “one or more”.

When a list of elements or characteristics is listed in this description, it means that the invention according to the invention "includes" or alternatively "is composed of" such elements.

Embodiments

Gas-chromatographic chemical analysis system with photoacoustic spectroscopy

With reference to Figures 1 to 4, the present embodiment refers to a chemical analysis system (portable) capable of identifying illegal or toxic trace substances (sub-ppm concentrations) thanks to the two-dimensional selectivity obtained from a specific combination between the Gas Chromatographic (GC) separation technique and the infrared (IR) photoacoustic (PA) analysis technique, in particular but not exclusively in its implementation called Quartz Enhanced Photo Acoustic Spectroscopy (QEPAS).

Referring to the discussion of the prior art, and in particular to the IRAS solution for the detection of toxic substances, the PA infrared photoacoustic technique generates spectra very similar (in shape and structural information contained) to the IRAS spectra, exploiting the pressure wave generated from a gaseous sample which, by absorbing the IR radiation, heats up and then expands generating an acoustic signal, which is then acquired by a special transducer, such as a microphone or a piezoelectric tuning fork. On the other hand, the photoacoustic technique can be implemented with solutions that allow you to analyze gaseous samples of infinitesimal volume. There are numerous implementations of the photoacoustic technique taken in itself, worthy of note is the technology of the company Gasera (Finland) which uses a silicon MEMS cantilever as a microphone for the acoustic wave (see for example: www.gasera.fi/technology/ optical-microphone /). A different and particular implementation of a photoacoustic system is the one that uses a quartz-enhanced photoacoustic spectroscopy QEPAS, using a variable wavelength IR laser beam (external cavity quantum cascade laser "EC-QCL") which is focused between the two prongs of the microdiapason. This allows to concentrate in that point, through which the entire mass of the concentrated sample packet to be analyzed passes, all the intensity of the infrared radiation. The QEPAS analyzer therefore appeared, according to the results of numerous tests carried out by the inventors, to be an infrared absorption analysis system that could be used effectively downstream of a gas-chromatographic separation column. However, these tests highlighted at the same time some criticalities and problems that required further experiments to find an adequate technical solution, as explained below.

According to the embodiment described here, the GC module is preferably implemented as a MEMS device of the FAST type, capable of separating even complex and not very volatile samples with reduced thermal budgets and very short elution times (a few minutes). However, the GC module can be any, and therefore not necessarily having the characteristics of the embodiment described below. Referring to Fig. 1, in the 1000 second system

the invention, the GC 100 module may include a

valve (for example 6 or 10-way) 104, to which I am

connected a pump for the sample 101, the tank of

carrier gas 103, a MEMS preconcentrator 160

(realized for example as in the embodiment of

GC shown below) and the actual GC column

150. From this GC column the gas packets pass to

QEPAS 200 module, which includes a fork (also

called “diapason”) piezoelectric 210 with resonator

in quartz and an infrared source 220.

In the overall system 1000 can also be

there is a pre-concentrator 300 in one stage

previous to the GC module. Such a pre-concentrator uses

a sample inlet 310, and a reversible pump

330 to pre-concentrate the same sample in 320 e

supply it to the GC 100 'stage.

With reference to figures 1 to 4, the QEPAS module

200 includes according to one aspect of the invention:

- an internal volume 210 of the cell 200;

- a micro-resonator 220 (or in general means

resonators);

- a piezoelectric fork 230 (or in general

transducer means) which transduces the signal

photoacoustic;

- a capillary GC 240 (coming or connecting

with the one coming out of the GC column); And

- optionally, holes for the insertion of means of

heating 250.

Although there are photoacoustic infrared analysis cells in the known art, the coupling with a gas-chromatographic column is achieved solely by the present invention, which specifies the modalities.

In fact, by coupling a photoacoustic cell 200 of the known art to a GC column (in itself also known) 100 ', the Inventors were able to observe an excessive dilution of the sample packets. In fact, known photoacoustic cells have an internal volume (in which to convey the sample packet to be analyzed) ranging from 100 to 1000 times the volume of a typical sample packet ranging from 10 to 100 microliters. Although the volume of the sample itself is variable, the packets leaving (eluted) from the GC column vary less than an order of magnitude, and therefore the packet would in any case find itself being strongly diluted and remixed with subsequent eluted packets. from the column, which would cancel any measurement of the peaks as illustrated below in concrete cases.

The inventors have instead been able to determine that if the volume of the cell reaches 10 times the volume of a packet, then this does not happen, it is still possible to measure the peaks and therefore to provide the appropriate analyzes. Even better is the situation where the cell volume reaches up to 5 times the volume of the packet, with a preference for the sub-range of up to 2, with which one is effectively able to process with high sensitivity and excellent selectivity. even very small steam flows, such as those delivered by a FAST-GC column.

One of the main applications of the present invention is aimed at the identification of multiple substances not known a priori, so the basic concept is that the smaller the internal volume of the cell, the better. Therefore, if the cell is not small enough, the measured peaks are too close and mix. Instead, the smaller the cell is compared to the sample packet, the more the cell performs multiple acquisitions following the peak. Ideally, the multiple acquisitions would constitute a quantitative measure of the substances detected, and not just a qualitative measure of the presence or absence of the same. However, since the main application is to detect the mere presence in the field, there is only an upper limit to the size of the cell, experimentally verified and reported above, and there is no lower limit of the same.

For this reason, thanks to the miniaturized internal volume, the concentration and separation of the chromatographic peaks is maintained inside the analysis chamber without dilution or mixing, thus allowing high sensitivity and identification of each component of the sampled mixture.

It can be seen from the above that for the purpose of coupling the parameters beyond the size of the internal volume are optional.

In relation to the type of substances to be analyzed, the inventors have identified a further problem generated by the known photoacoustic cells in some cases. In fact, the packets of samples of high boiling substances (or in general low volatile substances) are subject to condensation when they enter these cells, to such an extent as not to allow adequate detection of the peaks. For these substances, therefore, the simple coupling of the two prior art devices would degrade the measurement making the overall system unusable. This problem has been solved by equipping the photoacoustic cell with heating means for its internal volume, as well as optionally with heating control means.

The present embodiment therefore achieves an original and particularly effective coupling between separation and analysis devices and techniques, and gives rise to a new family of track sensors for field use which are distinguished by portability and response speed.

According to an embodiment, the core of the QEPAS detector is a heated detection chamber with a minimum dead volume. A laser beam is focused inside the chamber between the prongs of a standard commercial quartz (QTF) tuning fork that resonates at 32768 Hz, by means of a 25mm focal length external lens. In addition, a micro-resonator consisting of two small 0.9 mm I.D. and 4.6 mm in length is positioned close to the QTF to amplify the photoacoustic signal. The outlet of the GC column is connected to the chamber, which is heated to avoid condensation of less volatile compounds eluted from the column.

Another criticality detected by the Inventors during the coupling tests of the two devices is the distance between the outlet of the capillary from which the packets of the GC column come out and the point where the laser is focused, between the two branches of the detector fork. photoacoustic.

It was first of all possible to ascertain that the typical distance of a coupling between the devices of the known art, ie a distance ranging from 0.5 to 5 cm, does not allow an optimal measurement, because the dead volumes are still large. It has also been found that by reducing this distance in the 0.2 - 2 mm range, excellent measurements are obtained, and also excellent if you are below a millimeter (always due to less mixing and less dilution).

The inventors have tried a coupling with this reduced range both in the case of analysis volumes 100-1000 times the volume of the packets, and in the case of analysis volumes that do not exceed 10 times the volume of the packets. The result is that in the first case (of the known art) there is in any case no measurement, while in the second case the measurements are obtained and are excellent. In other words, varying the fork capillary distance alone does not solve the above dilution problem by itself.

In a practical embodiment, the QEPAS sensor uses an external cavity quantum cascade laser (EC-QCL), from Monolux Pranalytica (USA), as a tunable high brightness IR source from 8.8 μm to 9.9 μm, where different dangerous compounds have their own characteristic spectrum. The optical head of the QEPAS sensor (laser, focusing lens and QEPAS cell) is integrated with the electronics for signal reading and thermal control and with a mini-PC, which allows you to manage the module even remotely.

Since several target species are high-boiling compounds, the entire detection chain can be built to operate at elevated temperatures to avoid condensation. The injection valve can be a commercial 10-way valve (VICI-Valco) housed inside a small thermally insulated furnace and all tubes and transfer lines are heated by inserting them into polyimide tubes equipped with external steel metal braids stainless steel, which have been used as electrical resistors (Microlumen Inc., Oldsmar FL, USA).

The present embodiment is well combinable with the first embodiment described above (even if the combination is possible with any GC module), as the inventors have been able to ascertain with the results described below.

Miniaturized gas chromatographic system

The invention relates to a miniaturized gas-chromatographic system, based on MEMS components for the analysis of gaseous samples in traces by means of purge & trap thermal desorption preconcentration, in which the characteristics illustrated below can be included individually and in any combination, respecting the technical concept of the invention.

Referring to Fig. 5, the gas chromatographic device 100, in a first embodiment according to the invention, comprises a chromatographic column unit 150 and a preconcentrator 160 (also called "thermal desorption trap"). Mounted (for example as a bridge) between the two, there is an injector unit 140. The assembly preferably takes place through O-rings 180 which are squeezed between two rigid parts so as to form fluidic connections (more generally a any fluidic joints or connections, even using means other than O-rings). In the part between the preconcentrator 160 and the gas chromatographic column 150, a fluidic head 170, preferably in steel, faces the injector unit 140. Still, preferably, there is no direct contact between the fluidic head 170 and the injector unit 140, but the contact occurs through O-Ring 180.

The separator column is a column preferably included in the group which includes: packed micro-machined GC columns, semi-packed micro-machined GC columns, micro-machined capillary GC columns, micro-machined multi-capillary GC columns, porous layer tubular GC columns and columns Micro-processed GCs based on ionic liquids.

The thermal desorption trap 160 may be filled with a suitable absorbent from the set of porous polymers, graphite carbons, molecular sieves, molecular zeolite sieves, or multiple bed sorbent traps based on sequences of any of the aforementioned sorbents.

According to an advantageous embodiment, both the thermal desorption trap and the chromatographic separation column are both filled with graphite carbons with different specific surfaces, therefore they are suitable for high temperature ramps in the presence of oxygen in the carrier gas and thus allowing the use of purified air as a carrier gas.

On the other side with respect to the fluidic head 170, one or two layers of material 120,130 are mounted as a means interposed between the injector unit 140 and the solenoid valves 110. A first layer 130 is preferably made of aluminum and serves as a structural reinforcement and as a protection for a second layer 120 which is made of a thermally insulating material, so that the solenoid valves 110 do not heat up in contact with the injector unit 140.

Referring to Fig. 6, we see the fluid flows inside the device 100 of the invention. There are the inlet and outlet flows of the sample, the overpressure dP of the carrier gas, the underpressure -dP of the pump sucking the sample (or other means of handling the sample), as well as the outlet flow towards the detector, in this case indicated to be “PID” photo-ionization. Schematically, the overpressure dP pushes the carrier gas into the gas chromatographic column 150, gas which then passes into the injector unit 140 and finally into the detector (one or more, not shown). This circuit is operated through the use of solenoid valves 110 which, however, open and close other pressure actuated on / off valves, better illustrated below.

Referring now to Fig. 7, further details of the device are given, according to an embodiment of the invention.

The ducts that allow some of the various flows described are clearly seen. In particular, 173 indicates the inlet of the sample, with 171 the overpressure dP and 172 the underpressure -dP, with 174 the outlet towards the detector. The inlet channel 125 for the actuation pressure is formed in the thermally insulating layer 120. There are two other channels 135 between the solenoid valves 110 and the injector unit 140, which are actuation channels of the device (of the valves V1-V5, see below), which receive pressure from the channel 125. The channels 171-174 they are advantageously made in the fluidic head 170, and this is preferably made of steel: in fact this material has a high degree of passivation (i.e. it is possible to passivate the surface of the channels, for example with vitrification processes, so that they become inert). The gas, entering 173, is directed towards the injector, which sorts the flow through the actuation of valves V1-V5.

Finally, the solenoid valves 110 take electrical energy through wires 115.

In general, the injector, pipes and valves are included in the term "flow control means", which can be made in various ways.

Although the figures show O-rings 180 in the formation of some ducts, other means with the same function can be used in the device according to the invention. For example, gaskets or connections with metal alloys can be used, for example a fluidic joint based on molten metal (soft metallic seals). More generally speaking, therefore, fluidic junctions or sealing means for the O-rings or gaskets or the like.

It should also be noted that the gas chromatographic column 150, the preconcentrator 160 and the injection unit 140 are made as MEMS to provide a miniaturization to the device. In particular, the injection unit 140 functions both as an injector and as a fluidic manifold (connection) to interconnect to the preconcentrator and to the gas-chromatographic column, in order to minimize dead volumes while allowing to keep the entire analytical circuit crossed by the sample. at elevated temperatures (since MEMS valves are resistant to high temperatures), and thus optimize analytical performance.

Referring now to Figs. 8 and 9, the functional circuit of the device according to the invention is shown. In the specific example illustrated there are five on / off valves, but there may be more than five. These valves V1-V5 are preferably all in the injection unit 140.

The circuit in the state of Fig. 8 has three valves open and two closed, in order to create, thanks to the under pressure –dP, a flow in the preconcentrator 160 so that the analytes are concentrated there. The gas chromatographic column is in any case affected by a flow controlled by the overpressure dP, otherwise it can be subject to contamination.

At the end of this process, the closing / opening of the valves is reversed, so that from the pre-concentrator suitably heated to release the sample, the gas, pushed by the overpressure dP, passes to the gas chromatography column 150 and then to the detector (not shown). The MEMS valves are controlled by the group of solenoid valves 110. Fig. 10 exemplifies the operation of the MEMS valves. These on / off valves are preferably polymeric micro-membranes made between two silicon wafers.

The two pumps (or more generally means for moving gas or for creating pressure) for overpressure and underpressure are preferably different.

According to a different embodiment of the present invention, the pre-concentrator 160 is in thermal connection or integrates (making them for example as MEMS) one or more heaters and one or more temperature sensors (not shown). Same thing can be expected for the chromatographic column. By "thermal connection" we mean any connection (contact, radiant, etc .; internal or external) capable of conveying heat from the heater to the heated element (pre-concentrator and chromatographic column).

According to an aspect of the invention, a heater can also be provided for the fluidic head 170. For example, electric heaters in Kapton / Copper can be used, but it could also be done with simple resistors or armored glow plugs. At this point, it can be assumed that the MEMS injector chip 140 will be heated by radiation from the fluidics head 170, which is very close to it.

However, it is possible to add an additional Kapton / Copper film heater to directly heat the MEMS injector 140 chip, positioned between the MEMS 140 and the PEEK 120 block (generally an insulating material), or a heater integrated in the injector. same 140, as done for the pre-concentrator 160 and the chromatographic column 150.

According to an aspect of the present invention, the system can comprise in the injector 140 a sampling loop, to allow the alternate use of a thermal desorption trap or a sampling loop. In fact, if it is a question of analyzing a sample with a high concentration and it is therefore not necessary to enrich the sample through the pre-concentration process, it is possible to use loop injection which guarantees faster analyzes (not requiring additional cycles of pre-concentration and release) and more precisely controlled volumetric injections.

It should be noted here that in the known art there is no passage between the preconcentrator and the gas chromatographic column with pressure-actuated on-off valves. Furthermore, the valves are not all incorporated into a single component as in the present invention.

The fact that in the present invention the circuit valves have been decoupled from the solenoid valves makes it possible to work at high temperatures. It is thus possible to keep the MEMS injector at temperatures up to 250 ° C to avoid the condensation of high-boiling molecules, while implementing an injection system with almost zero dead volume. This makes the gas chromatography system general-purpose, unlike that described in [3] which was specific for the BTEX sample (benzene, toluene, ethylbenzene and xylene), which does not present condensation problems.

Furthermore, the fact that, unlike the injection of a loop, a MEMS pre-concentrator is used, has the advantage of increasing sensitivity.

Another feature of the system of the invention is that the MEMS injector effectively acts as a "microfluidic manifold" (which could also be called a "pneumatic motherboard" or "microfluidic motherboard") to interconnect the MEMS pre-concentrator to the column GC MEMS, thus creating a set of 3 MEMS interconnected directly facing each other (for example through micro-ORings), without the aid of additional components such as tubes / capillaries / manifolds. This allows to realize an extremely compact GC module, to further decrease the dead volumes and to keep the whole analytical chain at high working temperatures with a reduced energy consumption.

The detector is not specific to the present invention, as it could be any type of detector used in GC; we only mention, by way of example, the TCD (Thermal Conductivity Detector), the PID (Photoionization Detector), the FID (Flame Ionization Detector), the ECD (Electron Capture Detector), the PDD (Pulsed Discharge Detector), the MOX (Metal Oxide Detector), IMS (Ion Mobility Spectrometer Detector), MS (Mass Spectrometer Detector), IRAS (Infrared Absorption Detector), photoacoustic detectors, and electro-chemical sensors.

The system according to the invention can be used, according to the applications, with GC MEMS columns of different nature (capillaries, packed), which use inert carrier gases coming from cylinders (for example nitrogen, helium) or independently generated (for example hydrogen by electrolysis), or in some cases with simple filtered air.

The system according to the invention, comprising for example 3 MEMS (pre-concentrator, microfluidic injector / manifold, GC column), the solenoid valves (which are used only for the pressure actuation of the injector), the mounting supports, the heaters etc., measuring only a few cubic centimeters.

The system according to the invention can be used according to the following phases:

- operating said series of solenoid valves 110 so as to open and close the valves of said series of valves V1, V2, V3, V4, V5 to reach a first state in which said mixture of gas and sample is made to flow in said pre-concentrator 160 in such a way as to store said at least one analyte therein;

- regulating the temperature of said pre-concentrator 160 through said one or more pre-concentrator heaters and said one or more pre-concentrator temperature sensors;

- operating said series of solenoid valves 110 so as to open and close the valves of said series of valves V1, V2, V3, V4, V5 to reach a second state in which said at least one analyte is made to flow from said pre-concentrator 160 to said chromatographic separation column 150 and finally to said detector;

- adjusting the temperature of the chromatographic separation column 150 through said one or more separation column heaters and one or more separation column temperature sensors (this adjustment can also be partially superimposed on the phase leading to the second state); And

- activating said at least one detector and detecting the concentration of said at least one analyte.

The way in which to adjust the temperature in the two phases listed above, in order to obtain the gas chromatography analysis, is in itself known.

In a further not illustrated embodiment of the present invention, an analysis system is provided with a first and a second micro-machined gas chromatographic column in GCxGC configuration, as well as with a micro-machined modulator injector.

The modulator can implement two states of the fluidic system, where:

• in the first state of the fluidic system, the modulator implements a first fluidic circuit in which the separated sample eluted from the first GC column is accumulated inside a micro-fluidic circuit (microfluidic ring) while the second GC column elutes a sample using a pressure difference of the carrier gas;

• in the second state of the fluidic system, the modulator injects the eluted sample of the micro-fluidic ring into the second GC column by means of a pressure difference of the carrier gas.

The two states are implemented by the modulator again by means of a series of micro-machined valves, in which, again, the injector chip also acts as a pneumatic manifold by directly connecting the two GC columns.

Miniaturized gas-chromatographic system with photoacoustic spectroscopy - experiments and results The system according to the invention is used in an analysis method for gas-chromatographic separation and photoacoustic spectroscopy, including the execution of the following steps:

A. providing a gas chromatographic analysis system 100 in one of the embodiments described above;

B. operating said flow control means 140;

171, 172, 173, 174; V1, V2, V3, V4, V5 so as to reach said first state;

D. actuating said flow control means 140;

171, 172, 173, 174; V1, V2, V3, V4, V5 so as to reach said second state; And

F. operating said at least one photoacoustic detector 200 and identifying said at least one analyte.

According to one aspect of the invention:

- in phase B, operating said one or more solenoid valves 110 so as to open and close said one or more valves V1, V2, V3, V4, V5 to reach said first state;

- between phase B and phase D, the further phase C is performed in which to adjust the temperature of said preconcentrator 160 through said one or more pre-concentrator heaters and said one or more preconcentrator temperature sensors;

- in step D, operating said one or more solenoid valves 110 so as to open and close said one or more valves V1, V2, V3, V4, V5 to reach said second state; And

- between step D and step F, carrying out a further step E in which to adjust the temperature of said chromatographic separation column 150 through said one or more separation column heaters and one or more separation column temperature sensors.

The GC-QEPAS system was tested according to this method under laboratory conditions on a variety of nerve and blistering agent simulants, as reported in Table 1.

Table 1: simulants of nerve agents and vesicants used for laboratory validation

The test samples were prepared by evaporating a few microliters of the target species inside a 60 liter inner volume box and then sampling the contents of the box for periods ranging from 30 to 120 seconds. If we ideally assume the total vaporization of the injected liquid, it is possible to estimate the maximum concentrations in the range between a few ppm and a few tens of ppm. However, depending on the different volatility of the compounds tested and considering the partial condensation on the cold inner walls of the gas container, lower vapor concentrations are expected.

In addition, to simulate a typical pattern of volatile substances that are expected to interfere with measurement in real operating scenarios, saturation vapor concentrations of paints, diesel and petrol were added inside the gas container. Figure 11 shows a typical acquisition, including the integral absorbance chromatogram in (a) and the IR spectra of nerve agent simulants and blisters in (b), (c). Figure 12 shows the IR spectra of the other two nerve agent simulants. They were also identified by the GC-QEPAS sensor when sampled together with saturated gasoline vapors, which were successfully separated from the GC column prior to detection.

Advantages and applications of the invention

The present invention, which relates to a GC and photoacoustic analysis system, has, among others, the following advantages:

- excellent identification capacity: the photoacoustic spectra are very similar to the infrared absorption spectra and contain information on the functional groups of the molecules, so as to be able to distinguish cis-trans isomers;

- reduced weight, dimensions and consumption;

- more robust mechanics (no complex pumping systems for high vacuum are required) and less expensive (no turbo pump required); And

- shorter start-up, analysis and recovery times.

The invention also allows the extreme miniaturization of a purge & trap preconcentration system and subsequent (gas-) chromatographic separation of sample mixtures, thus allowing to obtain high sensitivity and high selectivity. The "all-MEMS" realization of the system, unlike the state of the art of miniaturized instruments, allows to work at higher temperatures, as all the components crossed by the sample are silicon based and therefore resistant to high temperatures, allowing the the same time to contain the times of a complete measurement cycle, from the initial sampling to the analysis result, in an interval of a few minutes, typically between 5 and 10 minutes. This makes it possible to analyze even high-boiling substances.

The invention can be used in the following fields, listed but not limited to: field analysis of complex samples; safety & security (explosives, CBRNe), industrial monitoring, monitoring of environments that are hazardous to the health of operators, biomedical analysis (e.g. breath analysis), environmental / air quality, indoor air quality, agri-food, monitoring of industrial processes, energy and natural gas ( quantification of odorants).

In the foregoing, the preferred embodiments have been described and variants of the present invention have been suggested, but it is to be understood that those skilled in the art will be able to make modifications and changes without thereby departing from the relative scope of protection, as defined by the claims attached.

Claims (19)

CLAIMS 1. System (1000) for analyzing a sample containing an analyte by gas chromatographic separation and photoacoustic spectroscopy, comprising: - means for moving a carrier gas; - a pre-concentrator (160); - a chromatographic separation column (150); - at least one detector (200) of said at least one analyte; - flow control means (140; 171, 172, 173, 174; V1, V2, V3, V4, V5) of a mixture of said sample and said carrier gas from the preconcentrator (160) to said at least one detector (200 ), said flow control means being configured for: In a first state, making said mixture flow in said pre-concentrator (160) in such a way as to store said at least one analyte therein; In a second state, let said at least one analyte flow from said pre-concentrator (160) to said chromatographic separation column (150), and finally to said detector (200) through a first capillary, from which they come out in the form of analyte packages; the system (1000) being characterized by the fact that the at least one detector (200) is at least one photoacoustic detector, comprising an internal volume (210) of a cell (200) of a photoacoustic detector; and wherein said internal volume (210) has dimensions less than 10 times the volume of said analyte packets. System (1000) according to claim 1, wherein said internal volume (210) has dimensions less than 5 times the volume of said analyte packets. System (1000) according to claim 2, wherein said gas-chromatographic separation column is a FAST column and said internal volume (210) has dimensions less than 2 times the volume of said analyte packets. System (1000) according to one or more of claims 1 to 3, wherein said photoacoustic detector cell (200) comprises heating means for said internal volume (210). System (1000) according to one or more of the preceding claims, wherein a second capillary (240) connected to said first capillary and configured to inject said at least one analyte into said internal volume (210) is included. System (1000) according to one or more of the preceding claims, wherein said at least one photoacoustic detector (200) comprises: - transducer means (230) having an excitation point of the photoacoustic signal and being configured to transduce a photoacoustic signal; And - resonator means (220) configured to amplify the photo-acoustic signal; and in which said first capillary or said second capillary (240) opens at a distance from the excitation point of the photoacoustic signal in the range 0.2-2 mm. System (1000) according to claim 6, wherein said distance is less than 1 mm. System (1000) according to claim 6 or 7, wherein the transducer means (230) includes a piezoelectric fork (230) with two branches, in which the excitation point of the photoacoustic signal is located between the two branches. System (1000) according to one or more of claims 1 to 8, wherein: - said chromatographic separation column (150) is in thermal connection with or integrates one or more separation column heaters and one or more separation column temperature sensors; and - said pre-concentrator (160) is in thermal connection with or integrates one or more pre-concentrator heaters and one or more pre-concentrator temperature sensors. System (1000) according to one or more of claims 1 to 9, wherein: - said flow control means comprise: � an injector (140) configured for the introduction of said sample coming out of said chromatographic separation column (150) in said at least one detector (200); � one or more valves (V1, V2, V3, V4, V5) positioned in respective points of said injector (140), - the pre-concentrator (160), the chromatographic separation column (150) and the injector (140) are made as MEMS; - said one or more valves (V1, V2, V3, V4, V5) are on-off valves made as MEMS inside said injector (140); And - said one or more valves (V1, V2, V3, V4, V5) are controlled by a set of solenoid valves (110) placed at a predetermined distance from them. System (1000) according to claim 10, in which a thickness of thermally insulating material (120) is interposed between the series of solenoid valves (110) and the series of valves (V1, V2, V3, V4, V5), to for example PEEK, and optionally between said thickness of thermally insulating material (120) and the series of valves (V1, V2, V3, V4, V5) a metal thickness is interposed. System (1000) according to one or more of the preceding claims, wherein said flow control means comprise a series of conduits (171, 172, 173, 174) configured and adapted to allow the flow of said mixture of carrier gas and of sample to be analyzed towards the injector (140), and in which said series of ducts (171, 172, 173, 174) includes fluidic junctions (180), for example in the form of O-rings, interposed between said injector (140 ) on the one hand, and said pre-concentrator (160) and said chromatographic separation column (150) on the other. System (1000) according to claim 12, wherein a fluidic head (170) is included, for example made of steel, which compresses said pre-concentrator (160) and said chromatographic separation column (150) on said injector (140 ) and which comprises said series of conduits (171, 172, 173, 174). System (1000) according to claim 12 or 13, wherein said fluidic head (170) comprises one or more fluidic head channels (171, 172) in said series of conduits (171, 172, 173, 174), configured and suitable for transmitting the pressure from said means for moving a carrier gas. System (1000) according to claim 10 and / or one or more of claims 11 to 14, when dependent on claim 10, in which a series of channels extend between the solenoid valves (110) and said injector (140) actuation (135) of said series of valves (V1, V2, V3, V4, V5). System (1000) according to one or more of claims 10 and / or one or more of claims 11 to 15, when dependent on claim 10, wherein said series of valves (V1, V2, V3, V4, V5) comprises at least 5 valves, in said first state three valves being open and two closed, and vice versa in said second state. System (1000) according to claim 10 and / or one or more of claims 11 to 16, when dependent on claim 10, wherein said injector (140) comprises a sampling ring or "loop" from which said sample, connected in such a way that, when used, it excludes said pre-concentrator (160). 18. Method of analysis for gas chromatographic separation and photoacoustic spectroscopy, including the execution of the following steps: A. providing a gas chromatographic analysis system (100) as defined by one or more of claims 1 to 17; B. actuating said flow control means (140; 171, 172, 173, 174; V1, V2, V3, V4, V5) so as to reach said first state; D. actuating said flow control means (140; 171, 172, 173, 174; V1, V2, V3, V4, V5) so as to reach said second state; And F. operating said at least one photoacoustic detector (200) and identifying said at least one analyte. Method according to claim 18, wherein in step A the system according to claims 9 and 10 is provided or according to one or more of claims 11 to 17 when dependent on claims 9 and 10, wherein: - in phase B, operating said one or more solenoid valves (110) so as to open and close said one or more valves (V1, V2, V3, V4, V5) to reach said first state; - between phase B and phase D, the further phase C is performed in which to adjust the temperature of said preconcentrator (160) through said one or more pre-concentrator heaters and said one or more preconcentrator temperature sensors; - in step D, operating said one or more solenoid valves (110) so as to open and close said one or more valves (V1, V2, V3, V4, V5) to reach said second state; And - between phase D and phase F, carry out a further phase E in which to adjust the temperature of said chromatographic separation column (150) through said one or more separation column heaters and one or more separation column temperature sensors .