spectroscopy of sample mixtures

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

Background art

Various types of portable chemical analysis systems capable of identifying illicit or toxic trace substances (sub-ppm concentrations) are generally known. However, such systems, in addition to having several limits, are cumbersome and therefore usable only in the laboratory.

The only type of equipment currently capable of taking measurements of this type in the field is based on the coupling between gas-chromatographic (GC) columns and mass spectrometers (MS) , as in the case of the Inficon Hapsite and the FLIR Griffin G510. However, the main defects of these mass spectrometers are the following:

1) they require complex and expensive pumping systems to create a high vacuum inside the spectrometer; 2) they have issues detecting substances with a molecular weight lower than 40, such as, for example, toxic gases such as ammonia and phosphine;

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

On the other hand, as it is known, instruments based on the coupling between GC separation techniques and techniques for analyzing the infrared absorption spectrum (IRAS = Infra-Red Absorption Spectroscopy) have an identification capacity at least comparable to, and sometimes superior than, GC-MS instruments. In particular, the GC-IRAS is the most flexible and powerful laboratory method for identifying drugs, designer drugs and precursors thereof [see 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, having the same functional groups, but specially modified so as not to be recognizable ("designer drugs") . To date, however, no portable GC-IRAS instruments are available, since conventional IRAS analyzers (both of the dispersive and of the Fourier transform type) operate with analysis cells of significant volume, which may not be coupled with miniaturized GC columns. In addition to this there is the fact that existing GC systems also have limits, which often affect the final measurement of the spectrometers.

In fact, pre-concentration systems of the "purge&trap" type are known, used to increase the concentration of a sample before injecting it into a gas-chromatographic (GC) columns for separating and detecting the analytes contained therein. These as well are implemented almost exclusively in laboratory measurement systems, and generally consist of tubes (made of metal or glass) filled with specific absorbent materials which, at room temperature or cooled down, retain the molecules of interest (analytes) from the flow of sample. This sampling and pre-concentration step may even be long (tens of minutes), so as to absorb a large quantity of sample. When enough sample has been collected, the tube is generally heated (and therefore, the contained absorbent material) , releasing the trapped molecules (thermal desorption) inside a flow of carrier gas. An attempt is made to perform this release in the shortest possible time, so that the molecules absorbed are released inside 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 material inside a volume of only 100 milliliters. The concentration factor is ideally lOOx.

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

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

On the other hand, MEMS (on-chip) injection systems for gas-chromatography exist, also referred to for micro-gas-chromatography (pGC) , which are based on pressure-actuated membrane valves made of polymeric materials (generally Kapton) (for example, MEMS injectors [2]) . The advantage of such types of injector are that :

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

2) they may 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, to date, all MEMS GC injectors 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 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 pre-concentration illustrated above and made by means of a totally different technology) . One of the Applicants (istituto IMM of Consiglio Nazionale delle Ricerche) has, in the past, developed and published a miniaturized/portable "mini-GC" system [3], based on the pre-concentration in a MEMS (therefore not in a glass or metal tube) , on the injection into a MEMS GC column, and on a detector (which may be of different types) . This system allows to perform the GC analysis of some low concentration samples by means of the pre-concentration step. The advantages of such solution are:

i. The pre-concentrator allows, for example, to analyze benzene up to concentrations of ppb fractions;

ii. The MEMS pre-concentrator may 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 adapted to focus on the sample at the head of the GC column by means of 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 by means of rapid heating.

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

a. significant internal dead volumes, which worsen the quality of the injection due to a dilution/diffusion of the sample, therefore 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 such temperature (therefore prevents many applications other than benzene analysis) .

In addition to the aforementioned publication, other ones exist, regarding pre-concentration in 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 miniaturizable and the injection is carried out with conventional valves, therefore it is not possible to heat them up to measure low volatile compounds, and, additionally, the dead volumes of the valves used thereby are too high.

Patent application US 4028932 A [7] describes an improved photoacoustic cell to be used in the analysis of solid and quasi-solid samples. The cell includes a sample containment chamber having a wall made of a clear transparent material. The sample containment chamber is connected to a microphone by means of a thin tube which makes the cell, which includes the chamber tube and the microphone, an acoustic resonant structure with a frequency within the response features of the microphone. In one embodiment, the cell is mounted with respect to a support structure so that different portions of the sample may be related, so that the cell may be advantageously used to analyze plates, paper or the like, originating from chromatographic techniques. The gas in US 4028932 A is however used as a transducer means of an acoustic signal generated by the sample which is stationary. Therefore, there is no movement of analyte packets as there are in gas-chromatography, and therefore the issues of the latter technique, which instead requires temporal and spatial separation between packets and sufficient concentration thereof, are not there .

Therefore, the need still remains 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, by using compact and highly efficient miniaturized GC systems, as well as economic and efficient spectrometric systems, to be used in the field and beyond.

Object and subject-matter of the invention

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

It is a further object of the present invention to provide a chemical analysis method via gas- chromatographic separation and spectroscopy which solves all or part of the issues of the prior art.

It is subject-matter of present invention a chemical analysis system and method via gas-chromatographic separation and spectroscopy according to the appended claims .

Detailed description of embodiments of the invention

List of Figures

The invention will now be described, by way of non limiting illustration, with particular reference to the drawings in the accompanying Figures, in which:

— Figure 1 shows a diagrammatic representation of the combined (gas-) chromatographic and photoacoustic system according to an embodiment of the present invention;

— Figure 2 shows a side section of the QEPAS photoacoustic cell according to an embodiment of the present invention;

— Figure 3 shows a vertical front section of the same cell in Figure 1;

— Figure 4 shows a horizontal section of the same cell in Figures 2 and 3;

— Figure 5 shows a side section diagram of an embodiment of the GC device in accordance with the invention;

— Figure 6 shows a simplified side section diagram, with indication of the flows, of the device in Figure 1;

— Figure 7 shows a more detailed three-dimensional view of the device in Figures 5 and 6; — Figure 8 shows a detailed functional diagram of the device according to Figure 7, in a first pre concentration operating state;

— Figure 9 shows a detailed functional diagram of the device according to Figure 7, in a second GC analysis operating state;

— Figure 10 shows the flow directions in an open (b) and closed (a) microvalve in an embodiment of the device according to the invention;

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

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

It is specified herein that elements of different embodiments may be combined together to provide further non-limited embodiments, while respecting the technical concept of the invention, as the average person skilled in the art intends it without issues from what has been described .

The present description further relates to the prior art for the implementation thereof, with respect to the detailed features not described, such as, for example, elements of lesser importance usually used in the prior art in solutions of the same type.

When an element is introduced, it is always meant that it may be "at least one" or "one or more".

When elements or features are listed in this description, it means that the finding in accordance with the invention "comprises" or alternatively "is composed of" such elements.

Embodiment s

Gas-chromatographic chemical analysis system with photoacoustic spectroscopy

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

With reference to the discussion of the prior art, and, in particular, to the IRAS solution for detecting toxic substances, the photoacoustic PA infrared technique generates very similar spectra (in shape and contained structural information) to the IRAS spectra, exploiting the pressure wave generated by a gaseous sample which, by absorbing the IR radiation, warms up and then expands generating an acoustic signal, which is then acquired by a special transducer, such as, for example, a microphone or a piezoelectric tuning fork. On the other hand, the photoacoustic technique may be implemented with solutions which allow to analyze gaseous samples of infinitesimal volume. Numerous implementations of the photoacoustic technique per se exist; noteworthy is the technology of the Gasera company (Finland) which uses a silicon MEMS cantilever as a microphone for the acoustic wave (see for example: ww . gasera , f1/technology/opt ical-mi erophone/ ) . A different and particular implementation of a photoacoustic system is instead that using a quartz enhanced photoacoustic spectroscopy QEPAS, utilizing a variable wavelength IR laser beam (external cavity quantum cascade laser "EC-QCL") which is focused between the two prongs of the micro-tuning fork. This allows to concentrate at that point, through which the whole mass of the concentrated packet of the sample to be analyzed passes, all the intensity of the infrared radiation. According to the results of numerous tests carried out by the Inventors, the QEPAS analyzer appeared to be an infrared absorption analysis system which may have been effectively used downstream of a gas-chromatographic separation column. However, such tests, at the same time, highlighted some criticalities and issues which required further experiments to find an adequate technical solution, as explained below.

According to the embodiment described herein, the GC module is preferably implemented as a MEMS device of the FAST type, capable of separating, with reduced thermal budgets and very short elution times (a few minutes), even complex and low-volatile samples. However, the GC module may be any, and therefore not necessarily having the features of the embodiment described below. With reference to Figure 1, in the system 1000 in accordance with the invention, the GC module 100' may comprise a valve (for example, a 6-way or 10-way one) 104, to which a pump for the sample 101, the carrier gas tank 103, a MEMS pre-concentrator 160 (constructed, for example, as in the embodiment of the GC illustrated below) and the actual GC column 150 are connected. From this GC column the gas packets pass to the QEPAS module 200, which comprises a piezoelectric fork (also referred to as a "tuning fork") 230 with a quartz resonator and an infrared source 260.

The fork 230 allows a particularly effective coupling with the GC, both by virtue of the extremely small query volume thereof (approx. 1 microliter) which allows to solve the equally small peaks eluted by the GC, and by virtue of the fork, being much more rigid than a membrane, not being affected by the disturbance due to the passage of the analyte packet in the flow or the variations in the flow (within certain determinable limits, for example, up to a few tens of seem) .

In the overall system 1000, a pre-concentrator 300 in a stage preceding the GC module may also be present. Such pre-concentrator uses a sample inlet 310, and a reversible pump 330 to pre-concentrate the sample itself in 320 and supply it to the GC stage 100' .

With reference to Figures 1 to 4, the QEPAS module 200 comprises, according to an aspect of the invention:

— - an inner volume 210 of the cell 200 (e.g., the entire inner volume of the cell) ;

— - a micro-resonator 220 (or, in general, resonator means) ;

— - a piezoelectric fork 230 (or, in general, transducer means) which transduces the photoacoustic signal;

— - a GC capillary 240 (originating from or in connection with that exiting the GC column) ; and

— optionally, holes for inserting heating means 250.

Even though photoacoustic infrared analysis cells exist in the prior art, the coupling with a gas- chromatographic column is carried out only by the present invention, which specifies the methods thereof.

In fact, by coupling a photoacoustic cell 200 of the prior art with a GC column (also known per se) 100', the Inventors were able to observe an excessive dilution of the sample packets. In fact, known photoacoustic cells have an inner volume (in which to convey the sample packet to be analyzed) which ranges from 100 to 1000 times the volume of a conventional sample packet ranging from 10 to 100 microliters. Even though the volume of the sample is variable per se, the packets exiting the GC column (eluted) vary by less than one order of magnitude, and therefore the packet would, in any case, be strongly diluted and mixed with the following packets eluted from the column, which would cancel any measurement of the peaks, as shown below in concrete cases . The Inventors were instead capable of determining that, if the cell volume reaches 10 times the volume of a packet, then this does not happen, and the peaks may still be measured and therefore the appropriate analyzes may be provided. Even better is the situation in which the cell volume reaches up to 5 times the packet volume, with a preference for the sub-range which reaches up to 2 times, with which it is actually possible to process, with high sensitivity and excellent selectivity, even very small vapor flows, such as those supplied by a FAST- GC column.

One of the main applications of the present invention is aimed at identifying multiple substances not known a priori, whereby the basic concept is that the smaller the inner volume of the cell is, the better. Therefore, if the cell is not small enough, the measured peaks are too close and mix again. Instead, the smaller the cell is with respect to the sample packet, the more the cell makes multiple acquisitions following the peak. Ideally, the multiple acquisitions would constitute a quantitative measure with regard to the detected substances, and not only qualitative about the presence or not thereof. Since however the main application is to detect the mere presence in the field, there is only one upper limit to the size of the cell, experimentally verified and reported above, and there is no lower limit thereof .

For this reason, by virtue of the miniaturized inner volume, the concentration and the separation of the chromatographic peaks is maintained inside the analysis chamber without dilution or mixing, thus allowing a high sensitivity and identification of each component of the sample mixture.

It may be seen from the foregoing that, for the purpose of the coupling, the parameters beyond the size of the inner volume are optional.

In relation to the type of substances to be analyzed, the Inventors have identified a further issue generated by the photoacoustic cells known in some cases. In fact, the sample packets of high-boiling substances (or, in general, low-volatile substances) are subject to condensation when they enter these cells, to an extent such not to allow an adequate detection of the peaks. Therefore, for these substances, the simple coupling of the two devices of the prior art would degrade the measurement making the overall system unusable. This issue was solved by providing the photoacoustic cell with means for heating the inner volume thereof, 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 trace sensors for field use which are distinguished by portability and response speed.

According to an exemplary 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 tuning fork (QTF) which resounds at 32,768 Hz, by means of a 25 mm focal length external lens. Furthermore, a micro-resonator consisting of two small steel tubes with a 0.9 mm I.D. and a 4.6 mm 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 tests for coupling the two apparatuses is the distance between the capillary outlet from which the packets of the GC column outlet and the point where the laser is focused, between the two branches of the photoacoustic detector fork.

First of all, it was possible to ascertain that the conventional distance of a coupling between the devices of the prior art, i.e., a distance ranging from 0.5 to 5 cm, does not allow an optimal measurement, since the dead volumes are still large. It has also been ascertained that, by reducing such distance to the range of 0.2 - 2 mm, optimal and even excellent measurements are obtained when staying below the millimeter (always due to less mixing and less dilution) .

The Inventors have tried a coupling in 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 which do not exceed 10 times the volume of the packets. The result is that, in the first case (of the prior art), there is still no measurement, while in the second case the measurements are obtained and are excellent. In other words, exclusively changing the fork capillary distance does not solve alone the dilution issue described above.

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 pm to 9.9 pm, in which different dangerous compounds have their characteristic spectrum. The optical head of the QEPAS sensor, (laser, focusing lens and QEPAS cell) , is integrated with the electronics for reading the signal and the thermal control and with a mini-PC, which allows to manage the module even remotely .

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

The present embodiment may be well combined with the first embodiment set out above (although the combination is possible with any GC module) , as the Inventors were 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 analyzing trace gaseous samples by means of purge&trap pre-concentration with thermal desorption, in which the features illustrated below may be understood individually as well as in any combination, respecting the technical concept of the invention.

With reference to Figure 5, the gas-chromatographic device 100, in a first embodiment according to the invention, comprises a chromatographic column unit 150 and a pre-concentrator 160 (also referred to as a "thermal desorption trap") . Mounted (for example, bridged) between the two, there is an injector unit 140. The mounting preferably occurs by means of O-rings 180 which are pressed between two rigid parts so as to form fluidic connections (more generally, any joint or fluidic connection, even using means other than O-rings, may be used) . In the part between the pre-concentrator 160 and the gas chromatographic column 150, a fluidic head 170, preferably made of steel, faces the injector unit 140. Again, preferably, there is no direct contact between the fluidic head 170 and the injector unit 140, but the contact occurs by means of O-Rings 180.

The separation column is a column preferably comprised in the group which includes: packed micro- fabricated GC columns, semi-packed micro-fabricated GC columns, micro-fabricated capillary GC columns, micro- fabricated multi-capillary GC columns, porous-layer tubular GC columns and micro-fabricated GC columns based on ionic liquids .

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

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

With reference to Figure 6, the fluid flows inside the device 100 of the invention are shown. There are the sample inlet and outlet flows, the overpressure +dP of the carrier gas, the underpressure -dP of the pump which sucks in the sample (or other sample movement means), as well as the outlet flow towards the detector, in this case meant to be a photoionization detector "PID". 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 by means of the use of the solenoid valves 110 which, however, open and close other pressure-actuated on/off valves, better illustrated below.

With reference now to Figure 7, further details of the device are given, according to an embodiment of the invention .

The pipes which allow some of the various flows described are clearly shown. In particular, 173 indicates the inlet of the sample, 171 the overpressure +dP and 172 the underpressure -dP, 174 the outlet towards the detector. In the thermally insulating layer 120 the actuation pressure inlet channel 125 is made. Two other channels 135 are there between the solenoid valves 110 and the injector unit 140, which are channels for actuating the device (for the valves V1-V5, see below), which receive pressure from the channel 125. The channels 171-174 are advantageously constructed 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 by actuating the valves V1-V5.

Finally, the solenoid valves 110 take electricity by means of the wires 115.

In general, the injector, the tubes and the valves are included in the term "flow control means", which may be constructed in various manners.

Although the Figures show O-rings 180 in the construction of some pipes, other means with the same function may be used in the device according to the invention. For example, gaskets or connections with metal alloys may be used, for example, a soft metal- based fluidic junction (soft metallic seals) . More generally, reference is therefore made to fluidic junctions or sealing means for the O-rings or gaskets or other .

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

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

The circuit in the state in Figure 8 has three open and two closed valves, so as to create, by virtue of the underpressure -dP, a flow in the pre-concentrator 160 so that precisely the analytes are concentrated there. The gas-chromatographic column is however affected by a flow controlled by the overpressure +dP, otherwise it may 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 for releasing the sample, the gas, pushed by the overpressure +dP, passes to the gas-chromatographic column 150 and then to the detector (not shown) . The MEMS valves are controlled by the group of solenoid valves 110. Figure 10 exemplifies the operation of the MEMS valves. Such on/off valves are preferably polymeric micro-membranes obtained between two silicon wafers.

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

According to a different embodiment of the present invention, the pre-concentrator 160 is in thermal connection or integrates (for example, constructing them as MEMS) one or more heaters and one or more temperature sensors (not shown) . The same thing may be expected for the chromatographic column. "Thermal connection" means 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 may also be included for the fluidic head 170. For example, electric Kapton/Copper heaters may be used, although, even simple resistors or armored glow plugs may work. At this point, it may be assumed that the injector MEMS chip 140 will be heated by radiation from the fluidic head 170, which is very close thereto.

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

According to an aspect of the present invention, the system may comprise in the injector 140 a sampling loop, to allow the use, alternatively, of a thermal desorption trap or of a sampling loop. In fact, if analyzing a high- concentration sample is required, and therefore enriching the sample by means of the pre-concentration process is not necessary, using the loop injection may be possible, which ensures faster analysis (not requiring additional pre-concentration and release cycles) and more precisely controlled volumetric injections .

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

The fact that, in the present invention, the circuit valves are decoupled from the solenoid valves allows to work at high temperature. 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 almost-zero dead volume injection system. This makes the gas-chromatography system general-purpose, unlike what has been described in [3] which was specific for the BTEX sample (benzene, toluene, ethylbenzene, and xylene) , which does not present condensation issues.

In addition, the fact that, unlike in the loop injection, 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 acts in all respects as a "microfluidic manifold" (which may also be referred to as a "pneumatic motherboard" or "microfluidic motherboard") to interconnect the MEMS pre-concentrator to the MEMS GC column, thus creating a set of 3 interconnected MEMS, directly facing them (for example by means of micro-O-rings ) towards one another, without the aid of additional components such as tubes/capillaries/manifolds. This allows to create an extremely compact GC module, to further decrease dead volumes and to keep the whole analytical chain at high working temperatures with reduced energy consumption.

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

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

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

The system in accordance with the invention may be used according to the following steps :

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

— the temperature of said pre-concentrator 160 is adjusted by means of said one or more pre concentrator heaters and said one or more pre concentrator temperature sensors;

— actuating said array of solenoid valves 110, so as to open and close the valves of said series of valves VI, 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 by means of said one or more separation column heaters and one or more separation column temperature sensors (this adjustment may also be partially superimposed on the step leading to the second state) , and

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

The way to adjust the temperature in the two steps listed above, so as to obtain the gas-chromatography analysis, is known per se.

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

The modulator may implement two states of the fluidic system, in which:

• 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 microfluidic circuit (microfluidic ring) while the second GC column elutes a sample using a carrier gas pressure difference;

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

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

Miniaturized gas-chromatographic system with photoacoustic spectroscopy - experiments and results

The system in accordance with the invention is used in an analysis method via gas-chromatographic separation and photoacoustic spectroscopy, comprising the following steps :

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

B. actuating said flow control means 140; 171, 172,

173, 174; VI, V2, V3, V4, V5 so as to achieve said first state;

D. actuating said flow control means 140; 171, 172,

173, 174; VI, V2, V3, V4, V5 so as to achieve said second state; and

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

According to an aspect of the invention:

— at step B, operating the aforesaid one or more solenoid valves 110 so as to open and close said one or more valves VI, V2, V3, V4, V5 for achieving said first state;

— between step B and step D, a further step C is carried out, in which the temperature of said pre- concentrator 160 is adjusted by means of said one or more pre-concentrator heaters and said one or more pre-concentrator temperature sensors;

— at step D, operating said one or more solenoid valves 110 so as to open and close said one or more valves VI, V2, V3, V4, V5 for achieving said second state; and

— between step D and step F, performing a further step E in which the temperature of said chromatographic separation column 150 is adjusted by means of said one or more separation column heaters and one or more separation column temperature sensors .

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

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

The test samples were prepared by evaporating some microliters of the target species inside a box of 60 liters of inner volume and then sampling the contents of the box for periods between 30 and 120 seconds. Ideally assuming 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 tested compounds and considering the partial condensation on the cold inner walls of the gas container, lower vapor concentrations are expected.

In addition, to simulate a conventional model of volatile substances which are expected to interfere with the measurement in real operating scenarios, paint, diesel, and gasoline saturation vapor concentrations have been added to the gas container. Figure 11 shows a typical acquisition, including the integral absorbance chromatogram in (a) and the IR spectra of nerve and blistering agent simulants in (b) , (c) . Figure 12 shows the IR spectra of the other two nerve agent simulants. They were identified by the GC-QEPAS sensor even when sampled together with gasoline-saturated 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, such to be capable of distinguishing cis-trans isomers;

— reduced weights, size, and consumption;

— mechanics being more robust (complex pumping systems for high vacuum are not required) and less expensive (no turbo pump required) ; and

— shorter start up, analysis and recovery times.

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

The invention may be used in the following fields, not listed by way of limitation: field analysis of complex samples; safety&security (explosives, CBRNe) , industrial monitoring, monitoring of environments hazardous for the health of the operators, biomedical analysis (e.g., breath analysis), environmental/air quality, indoor air quality, agro-food, industrial process monitoring, energy and natural gas (odorant quantification) .

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In the foregoing, the preferred embodiments have been described and variants of the present invention have been suggested, however it is to be understood that those skilled in the art will be able to modify and change them without departing from the related scope of protection, as defined by the appended claims