Open Probe Fast GC-MS - Real Time Analysis with Separation

Uri Keshet (1), Tal Alon (1,2) , Alexander B. Fialkov (1), and Aviv Amirav (1,2) 

1.   School of Chemistry, Tel Aviv University, Tel Aviv 69978, Israel.  

2.   Aviv Analytical Ltd, 3 Haarad Street, Tel Aviv 69107, Israel  

Abstract 

An Open Probe inlet was combined with a low thermal mass (LTM) ultra fast gas chromatograph (GC) and a mass spectrometer (MS) of a standard GC-MS for obtaining real time analysis with separation. The Open Probe is based on a vaporization oven that is open to room air with an addition of helium purge flow protection that eliminates air leakage into the oven, column and MS ion source. Sample introduction into the Open Probe is as simple as; touch the sample, insert the sample holder into the open probe oven and have the results in 30 s with under a minute ready for next analysis. 

The Open Probe Fast GC-MS revolutionizes the field of real time analysis as it provides several major benefits in comparison with DART, DESI and other ambient ionization methods or MS probes:

• GC separation,
• Library identification
• Absence of ion suppression effects
• Uniform electron ionization response for improved quantitation
• Uses a low cost quadrupole MS (of GC-MS). 

Watch the short video below and keep reading to find out more about the new Open Probe fast GC-MS which was combined with Agilent 7890B GC and 5977 MS and learn about its several demonstrated application and benefits. 

If the video doesn't show, you can click here to see it on Youtube.

Introduction 

Recently, Desorption Electrospray Ionization (DESI) [1], Direct Analysis in Real Time (DART) [2], Atmospheric Solids Analysis Probe (ASAP) [3] Direct Sample Analysis (DSA) [4] and similar techniques as reviewed in [5, 6] and references therein have received significant attention and publicity as new methods that allow fast organic surface analysis, without sample preparation, through ambient pressure ionization and ion transfer into the mass spectrometer through an ion funnel as used in LC-MS systems. However, these techniques suffer from highly non-uniform response, are ineffective with several groups of compounds, suffer from hard to predict ion suppression effects and do not share the extensive mass spectral information and library identification strength of electron ionization. Furthermore, in view of lack of chromatographic separation they require expensive high resolution MS instrumentation of LC-MS for most of their applications (since most samples are in mixtures) and cannot use the lower cost MS of GC-MS instruments without major and expensive modifications. 

Our group's first attempt at direct analysis in real time started about 16 years ago in our experiments with laser desorption ultra fast GC-MS with supersonic molecular beams [7]. In these experiments that preceded in several years the earliest DESI and DART experiments, a laser was used to desorb organic compounds from a variety of surfaces without sample preparation followed by helium sweeping and ultra fast (few seconds) GC separation and either electron ionization or hyperthermal surface ionization MS analysis.   

However, despite the many approaches for probe and probe like "direct analysis in real time" and in view of their limitations there is a growing need for a simple MS based device that will allow real time analysis with a cycle time of sub one minute, that will be combined with ultra-fast separation, enable automated library identification, will have uniform response for appropriate quantitation and that will be sensitive, inexpensive and could use a low cost mass spectrometer.    

Open Probe Fast GC-MS System Description and its Operation   

A schematic diagram of the Open Probe fast GC-MS and a photo of sample introduction are shown in Figure 1. The full system is composed of three separate technologies that are grouped together: a) Open Probe which is described in details in references [8, 9]; b) Low thermal mass ultra fast GC which is described in details in references [10, 11] and; c) A quadrupole mass spectrometer of GC-MS. This mass spectrometer can be either of GC-MS with Cold EI as described in details in reference [12], or a standard Agilent model 5977 MSD with its standard in-vacuum EI ion source as describe with several examples in this article, or it can be the MS of the Aviv Analytical model 5975-SMB GC-MS with Cold EI (Aviv Analytical LTD, Tel Aviv Israel). GC-MS with Cold EI is reviewed in reference [13]. 

Figure 1. A schematic diagram of the Open Probe Fast GC-MS and a photo (bottom right side) demonstrating sample introduction using a melting point vial. The various components of the systems are indicated with names. In the photo, 1 is the melting point sample holder, 2 is the Open Probe, 3 is the LTM Fast GC and 4 is the standard GC (Agilent 7890B) of the Agilent 5977 GC-MS. 

As shown in Figure 1, the Open Probe comprises a heated Open Probe oven which is mounted on the low thermal mass (LTM) fast GC. The LTM fast GC with the Open Probe are connected to the mass spectrometer ion source through the GC oven, which serves as a heated transfer line. The Open Probe further includes an internal inert glass tube liner (5 mm ID and 6.35 mm OD) which is sealed by a Viton O-ring at the cooler input side and a helium gas supply line. An auxiliary helium gas line with its miniaturized pressure regulator and frit flow control element (not shown) serves to provide the needed helium flow rate. A small micro pump followed by a solenoid valve serves to pump the split gas line to reduce the injection time via the increase of the liner flow rate from 3 ml/min column flow rate to 15 ml/min total column and split flow rates, resulting in a split ratio of 5.

The main and most important novel feature of the Open Probe [8, 9] is that its oven is open to ambient air pressure to ease sample insertion while it can be sealed when not in use. Despite being open to ambient air, the air-sensitive GC column, ion source filament and delicate samples at the Open Probe's hot oven are protected from air by the gas purge protector element. The total helium gas flow rate is divided between a portion that flows through the fast GC column and a portion that purges the Open Probe oven through the purge gas protector, thereby eliminating air presence in the system. In a typical operation of the Open Probe fast GC-MS about 3 ml/min are used as the fast GC carrier gas, 12 ml/min as split flow rate and 60 ml/min as purge protection flow rate outside (total flow rate of 75 ml/min). The Open Probe liner is a half length standard GC injector liner with 5 mm ID and 39 mm length (Restek, Bellefonte PA, USA). The Open Probe also has a narrow thermal neck before its opening to the room air environment that serves as a thermal conductivity barrier to reduce the probe opening temperature as a safety mechanism that ensures that the user will not accidentally touch a hot surface during sample introduction. 

The Fast GC column (0.25 mm ID, 0.1 µ HT1 film) ends either in a union such as the Agilent Ultimate union or directly in the MSD transfer line and ion source and in that case its length is 2 m. The column flow rate is 4 ml/min while the GC column as at 60°C and 2.4 ml/min when the column is at 340°C when 0.25 mm ID column is used. The union can be connected with a flow restriction transfer line with 0.18 mm ID to reduce the column flow rate by about a factor of 2.     

Sample introduction can be performed in several ways, including via standard miniature ChromatoProbe vials or with inert swabs. However, we found that the use of a small thin walled glass tubes in the form of easily available disposable melting point vials is especially useful and easy to use. The typical melting point vials that we used were with 1.54 mm diameter 1.1 mm I.D. and 10 cm long (Wilmad Labglass, Vineland NJ USA). We found these vials also to be surprisingly flexible as they could be bent a little without breaking. The method of sample introduction into the Open Probe with these vials comprises the following steps: (a) the sample powder is lightly touched by the external bottom surface of the closed side of the glass vial; (b) the glass tube vial with the sample is manually inserted into the heated Open Probe oven and the sample is quickly (sub one second) vaporized since the thin walled glass tube has low thermal mass; (c) the sample vapor is swept by the helium gas flow into the capillary column of the fast GC and after separation it is transferred into the ion source where the sample is ionized and mass analyzed. The melting point vials can also be roughened via the use of a file and in that case it can be used with relatively hard surfaces such as of medical pills. The melting point vial can also be used in its open tube side via dipping it in acetone or methanol and touching the sample surface while wetting it with the solvent that soften it and or dissolve it for easier sampling. 

Our LTM fast GC is described in details in reference [10, 11]. It is based on a short piece of standard fused silica GC capillary column which is inserted into a low thermal mass metal tube that is resistively heated and that possesses an inlet and an outlet, both of which are connected to a current programmed power supply. The current program of the power supply provides a temperature program (with time). The temperature is measured via the resistance of the metal tube which increases with its temperature in a known manner. The capillary column in its resistively heated metal tube is mostly located in an air-cooled enclosure which is mounted instead of a detector on the top plate of the standard GC oven (Agilent 7890B GC in the experiments below). The outlet assembly of the heated metal tube is located at the inner edge of the standard GC oven housing so that the portion of it that is not resistively heated (about 1 cm) is heated to the standard GC oven temperature. In our experiments we used 1.3 m, 1.27 mm ID, 1.56 mm OD (1/16") stainless steel metal tube as the heating tube and 2 m standard 0.25 mm ID GC column with 0.1 µ PDMS film (Agilent DB-1HT). The LTM fast GC is capable of temperature program rate in excess of 1200ºC/min but our standard temperature program rates were typically 200-600ºC/min. The temperature program was achieved by current program of an external power supply in the 0-8A range and the temperatures were in the 60-340ºC range. 

The Agilent 5977 mass spectrometer was used as is with its extractor EI ion source, at 280°C transfer line temperature, 250-280°C ion source temperature and 6250 amu/s scan speed which was about 14 Hz scan speed in the 50-500 amu mass spectral range.

Results

Typical operation and use of the Open Probe fast GC-MS is demonstrated in Figure 2 in the real time analysis with separation of Heroin in its street drug powder. We used a standard melting point vial that lightly touched the Heroin powder and was inserted into the Open Probe while pressing the start button. The resulting total ion mass chromatogram is shown at the upper trace in Figure 2. As demonstrated, the gas chromatography separation took only 30 seconds and after 45 seconds the system was ready for the next analysis (under 15 seconds 340°C to 60°C cooling time). We note that the separation was reasonably good for the purpose of Heroin analysis and all the major Heroin street drug powder components were properly separated and could be quantified in terms of their % in the powder. Street drug Heroin is a white-gray powder that includes mostly the additives of acetaminophen and caffeine (total of about 80%) as well as the Heroin side product of 6-monoacetylmorphine and naturally occurring papaverine and noscapine (the last to elute peak). The standard EI mass spectrum of Heroin itself is shown at the bottom trace in Figure 2 and its NIST library matching factor was 932 and the NIST library identification probability was 95.3%. This library identification was further confirmed by our TAMI Molecule Identification software that is based on isotope abundance analysis [14] with exceptionally high 999 matching factor. Thus, the identification of Heroin as diacetylmorphine is unambiguous and assured in a legally acceptable way. Unique to the use of NIST EI library for sample identification is that it provides the sample name and structure (as shown in Figure 2) at the isomer structural level, which is not possible with high resolution MS alone. Furthermore, unique to the Open Probe fast GC-MS among all other real time analysis methods is the fact that we can use the Agilent Chemstation chromatography percent report and conclude that the street drug powder contains about 9% Heroin. This finding could be forensically important both for Heroin source identification and for knowing how much real drug is there in a given catch. We note that while the full analysis cycle time was 45 seconds it is considered real time since this time is comparable to the unavoidable sample handling time, namely taking the sample from its container, typing the sample name and details, touching the sample, introducing it into the Open Probe and performing data analysis. Moreover, the addition of a separation step simplifies and speeds up the data analysis process, thus could result in an overall faster analysis than with other real time analysis methods. 

Figure 2. Real time analysis of Heroin street drug powder by Open Probe fast GC-MS. The upper trace shows the obtained full scan total ion count mass chromatogram and the bottom trace shows the standard EI mass spectrum of Heroin itself. The data collection was continuous and sample injection was at 11.5 min after several other sample injections and as seen the chromatography practically ended after 30s.     

In Figure 3 we show the analysis of Cannabis flowers with the Open Probe fast GC-MS. Unique to this Cannabis flower analysis is the fact that it was very short and did not involve any sample preparation. The standard melting point vial lightly and gently touched once the Cannabis flower and was inserted into the Open Probe while pressing the start button and the resulting total ion mass chromatogram is shown at the upper trace of Figure 3. As demonstrated, the GC separation took only 30 seconds and in 50 seconds the system was ready for the next analysis. We note that the separation was reasonably good for the purpose of Cannabis analysis for the presence of its most important active ingredient of Tetrahydrocannabinol (THC) and Cannabinol (CBN) that are indicated by arrows in Figure 3. The standard EI mass spectrum of THC itself is shown at the bottom trace in Figure 3 and its NIST library matching factor was 953 and the NIST library identification probability was 93.2%. This identification was further confirmed by our TAMI Molecule Identification software that is based on isotope abundance analysis [14] with 999 matching factor. Thus, the identification of THC is unambiguous and assured in a legally acceptable way. We note that unique to the Open Probe Fast GC-MS among all other MS Probes and ambient ionization method is that the NIST library identifies THC at its isomer level as DELTA 9-Tetrahydrocannabinol, and lists all its commonly usded names starting with Dronabinol.   

Figure 3. The analysis of Cannabis flower by Open Probe fast GC-MS. The upper trace shows the obtained full scan total ion count mass chromatogram with arrows indicating the elution of its main active ingredients of THC and CBN and the bottom trace shows the standard EI mass spectrum of THC itself and the obtain NIST library identification data and THC structure. The data collection started with the pressing of the MS start button and the chromatography ended after 30 seconds. 

For the demonstration of the system's sensitivity, a volunteer briefly touched a TNT particle with two of his fingers and then dropped it. One finger then touched a clean glass beaker surface 51 times on different locations. A melting point glass vial touched the glass area of the 51st finger print and was inserted into the Open Probe for the TNT sample thermal desorption. The obtained total ion count mass chromatogram is shown in Figure 4 (upper trace) with a clear TIC peak of the TNT that was identified by the NIST library with 746 matching factor, 872 reversed matching factor and 85% identification probability. This analysis was performed with simultaneous full scan and SIM modes and the obtained SIM trace on m/z=210 of TNT is shown at the bottom trace of Figure 4. The Agilent Chemstation measured signal to noise ratio is 13000 in peak to peak when early chromatography time is considered for the noise and several thousand near the TNT peak. We also note that this way of analysis the human fingerprint wax compounds are reduced compared to the target TNT as can be observed in comparison with another Open Probe analysis of TNT on human hand [15]. The TNT separation time by the Open Probe fast GC was 40 s and the full analysis cycle time was 55s. 

Figure 4. Open Probe fast GC-MS analysis of TNT on glass surface that was touch by a tester's finger that previously touched other glass surfaces 51 times. The upper trace shows the obtained full scan total ion count mass chromatogram while the bottom trace shows the simultaneously measures SIM trace on the main TNT EI-MS peak of m/z=210. The S/N of the SIM trace is 13000 in peak to peak. 

In Figure 5 we demonstrate the analysis of Canola oil by the Open Probe fast GC-MS. The oil was lightly touched by the melting point vial on its closed end and it was wiped by a clean paper (to reduce the analyzed amount) and inserted into the Open Probe while touching the Open Probe Fast GC start button. As demonstrated an informative and characteristic TIC mass chromatogram is shown at the upper trace of Figure 5 while a relatively clean EI mass spectrum of Vitamin E is shown at the bottom trace. Unique to Open Probe Fast GC-MS is the fact that like in GC-MS the Vitamin E was identified by the NIST library as α Tocopherol among its ten isomers and structures and this form is the most biologically active. As further shown in Figure 5 we also found λ Tocopherol as another form of Vitamin E plus several other main ingredients of Canola oil including sterols such as γ Sitosterol. The highest peak shown in the TIC is of the C18 free fatty acids that coeluted (Oleic, linoleic and stearic). The ratio of these free fatty acids can serve as a finger print identification of the oil type. The oil chromatography shown took 40 seconds but di and triglycerides further eluted for a minute after that time as they entered the insufficiently hot transfer line (280°C).

Figure 5. Open Probe fast GC-MS analysis Canola oil. The upper trace shows the obtained full scan total ion count mass chromatogram while the bottom trace shows the EI mass spectrum of Vitamin E in the form of α Tocopherol which is one of its main ten forms and the biologically most active form (λ was also found and is indicated by an arrow).  

In Figure 6 we demonstrate the analysis of Olive oil by the Open Probe fast GC-MS and compare it with similar real time Olive oil analysis by the PerkinElmer DSA with high resolution TOF. The oil was lightly touched by the melting point vial on its closed end and it was wiped by a clean paper to reduce the analyzed amount and inserted into the Open Probe while touching the start button. As demonstrated an informative and characteristic TIC mass chromatogram is shown at the upper trace of Figure 6 while a high quality EI mass spectrum of γ Sitosterol is shown at the middle trace. The biggest TIC peak is of Squalene while the TIC peak before it is of the co-eluting three C18 free fatty acids (Oleic, Linoleic and Stearic) whose ratios can serve for the study of olive oil adulteration. The oil chromatography shown took 40 seconds but di and triglycerides further eluted for about a minute after that time as they entered the insufficiently hot transfer line (280°C). The bottom trace shows the PerkinElmer DSA results that were zoomed at the 360-460 amu mass spectral range while illuminating MS peaks of compounds with importance.

Figure 6. Open Probe fast GC-MS analysis Olive oil and its comparison with the PerkinElmer DSA Ambient Ionization analysis. The upper trace shows the obtained full scan total ion count mass chromatogram, the middle trace shows the EI mass spectrum γ Sitosterol. The bottom trace was taken from PerkinElmer published data of their DSA analysis of Olive oil with their high resolution TOF.

In the comparison of Open Probe Fast GC-MS and DSA as a different real time analysis method we mention the following differences:

1. In the Open Probe Fast GC-MS γ Sitosterol was identified by the NIST library with 74% identification probability while β Sitosterol was number 2 in the NIST hit list with 19.8% identification probability. The DSA trace claims that it is β Sitosterol but clearly DSA has no possibility to identify isomers and its claim is just a guess. Furthermore, the NIST library includes 25 compounds with elemental formula of C29H50O and high resolution TOF is incapable of distinguishing between them. Only the combination of having GC separation and NIST library identification can provide valuable isomer information. 
2. The DSA analysis unlike EI with the Open Probe Fast GC-MS provided masses that are not trivial to analyze as they are not of the compounds but of the compounds plus H and minus H2O and this mass can also be from a compound with the sterol molecular weight minus 18. 
3. The DSA response is highly non uniform hence unlike EI it cannot provide any quantitative estimate for the relative amounts of compounds in the oil.
4. While the DSA data shows some compounds it does not disclose the amount of time that should be devoted for the interpretation of the data. If the compounds are target compounds it can be a short time while if this is an unknown mixture it could be much longer than the analysis time. Open Probe Fast GC-MS data analysis is much simpler. 
5. DSA, DART and other ambient ionization techniques excel in the analysis of organic compounds on surfaces. If the Olive oil is found as liquid it can be quickly diluted and flow injected for its fast analysis by any standard LC-MS. However, when the oil is on a surface with Open Probe Fast GC-MS its sample handling is very easy, just touch the surface with the melting point vial and insert it into the Open Probe oven while such sample handling with DSA or DART is more complicated and time consuming.            

As shown and demonstrated above, the added dimension of separation is very useful for highly improved identification and quantitation and its added analysis time is very small. However, in rare cases one would like to give up the separation for further faster analysis. The conversion of Open Probe Fast GC-MS into an even faster Probe MS is simply achieved by maintaining the GC column at a constant high temperature such as 300°C and in this case the column is a part of the transfer line. With 2 m column and 3 ml/min flow rate the void time is 45 times faster than in standard GC-MS and thus it is only 2 seconds. Consequently, upon the insertion of a sample into the Open Probe while the 5977 is collecting data, after 2 seconds a peak appears of all the inserted compounds without or with very little separation. In Figure 7 we demonstrate the use of the Open Probe Fast GC-MS as a MS Probe via the insertion of the melting point vial after it lightly touched Ibuprofen powder and then after it touched Estradiol powder. The GC column and transfer line were maintained at 280°C. We started data collection with the 5977 and as indicated by an arrow at 0.40 min we inserted the Ibuprofen sample while after 0.8 min we inserted the Estradiol sample. As shown, both compounds appeared 3 and 4 seconds after their insertion with only little (1-2 s) delay by the GC column. The peaks were of the clean drug and steroid compounds and the obtained EI mass spectra and NIST library structures are shown in the inserts of Figure 7. The NIST library identification probabilities were 82.4% for Ibuprofen and 93.5% for Estradiol. Thus, if desirable the Open Probe Fast GC-MS can be effectively operated as an MS Probe with only few seconds analysis time. However, we believe that the merit of GC separation is so high that this mode will be rarely used and that it will be considered only when analysis times below 10 seconds could be needed.   

Figure 7. Open Probe Fast GC-MS operation as a MS Probe. The GC column and transfer line were maintained at 280°C and Ibuprofen was inserted at 0.40 min while Estradiol was inserted at 0.8 min after starting data collection with the 5977.  As shown, both compounds appeared 3 and 4 seconds after their insertion with only little (1-2 s) delay by the GC column. The obtained EI mass spectra and resulted NIST library structures are given in the inserts. As demonstrated, the Open Probe Fast GC-MS can be effectively operated as MS Probe with only few seconds analysis time. 

Another important feature of the Open Probe Fast GC-MS is the range of compounds amenable for analysis by the system. In order to explore the size limit we tested it in the analysis of a large polar drug such as Reserpine which is the LC-MS industry standard test compound but which is incompatible with standard GC-MS analysis as it does not elute from the standard GC-MS 30 m long column. As demonstrated in Figure 8 below, Reserpine can be analyzed by the Open Probe Fast GC-MS and it gives a nice and informative EI mass spectrum which is library searchable. As shown in the TIC mass chromatogram Reserpine eluted after the end of the Fast GC temperature program (340°C) since the transfer line temperature was at 280°C but this temperature can be increased. The reason for the ability to analyze extended range of compounds in comparison with standard GC-MS is the use of short (1.3 m) column with high (3 ml/min) column flow rate and thin 0.1µ film. In comparison with DESI, DART and DSA we note that Open Probe Fast GC-MS can also analyze non-polar compounds and compounds with low or no proton affinity. Obviously, when Cold EI is used instead of standard EI the range of compounds amenable for analysis is further increased as ion source related degradation and tailing is eliminated and the column flow rate can be further increased. 

        

Figure 8. Open Probe fast GC-MS analysis Reserpine. The upper trace shows the obtained full scan total ion count mass chromatogram while the bottom trace shows the EI mass spectrum of Reserpine with dominant molecular ion at m/z=608.

Any technology and Open Probe Fast GC-MS is also evaluated in its sensitivity. In this case the sensitivity is actually known even without testing since it is close to that of the Agilent 5977 with its extractor ion source that is claimed by Agilent to have about one femtogram limit of detection for Octafluoronaphthalene (OFN). We evaluated the Open Probe fast GC-MS sensitivity via the use of hexane solutions of Pyrene at 50 ppb concentration. We dripped with a syringe 1 µL of this solution that contained 50 pg Pyrene onto a melting point vial at its closed end, we dried it in room air for a few seconds and inserted it into the Open Probe for its fast GC-MS analysis with splitless injection. We inevitably obtained a mass chromatogram with a few peaks of hexane impurities and Open Probe oven contaminations and memory even in single ion monitoring mode at m/z=202 (Pyrene molecular ion). However, the Pyrene peak was easy to identify (indicated by arrow) by the NIST library and the SIM signal to noise ratio (in peak-to-peak) was over 80,000 in the SIM mass chromatogram when the noise was collected at the beginning of the SIM mass chromatogram. Thus, we conclude that the system instrumental detection limits of the Open Probe fast GC-MS is at the low femtogram range. However, as shown in the full scan trace the real limit of detection is determined by matrix interference effects and in this case in comparison with other MS Probes and ambient ionization techniques the addition of Fast GC improves the real LOD by the GC peak capacity which is over 100 as our typical peak width are about 0.25 s and chromatography time is 30 s. One reason why we selected Pyrene as our compound of choice for the evaluation of LOD is that Pyrene like other PAHs and many other compounds with low or negative proton affinities can not be properly analyzed by DESI and or DART/DSA thus our Pyrene sensitivity is in marked contrast with the poor DART, DSA and DESI sensitivity for such a compound.   

Figure 9. Open Probe fast GC-MS analysis of 50 picograms of Pyrene for the evaluation of the system sensitivity and limits of detection. The upper trace shows the obtained full scan total ion count mass chromatogram while the bottom trace shows the simultaneously obtain single ion monitoring (SIM) trace of Pyrene at its molecular ion m/z = 202 that resulted in signal to noise ration of over 80,000 in peak to peak.  

Discussion and Summary of the Open Probe Fast GC-MS Features 

Open Probe fast GC-MS is a new type of real time analysis method and device for enabling real time analysis with separation. In this article we demonstrated the operation of the Open Probe Fast GC which was coupled with a standard GC-MS, while in our recently published article [15] its operation with GC-MS with Cold EI (SMB) was described and demonstrated with several applications. Here we demonstrated, again, that ultra-fast chromatographic separation of 20-30 seconds can be achieved and while it doesn't add much to the overall analysis time, it provides valuable separation for improved identification and quantitation. Thus, the addition of separation extends the capabilities of real time analysis to samples in complex mixtures. Currently, the area of real time analysis is dominated by techniques such as DART, DESI, ASAP, DSA etc. In comparison with all these technologies the Open Probe fast GC-MS is characterized by the following major unique features and advantages: 

1. Real time Analysis with Separation. It provides sub one minute full analysis cycle time combined with separation. Considering the fact that sample handling and registration unavoidably takes about or more than a minute this is real time analysis yet with ultra-fast GC separation. As we hope that you could see, the separation helps in sample identification and in its quantitation. If the need arises one can also maintain the fast GC column at a high temperature and thus eliminate the separation to obtain an analysis time of a few seconds.
2. Library based sample identification. The use of EI library such as NIST uniquely provides sample identification including at the isomer level, with sample names and structures. Library based identification can also be combined with AMDIS deconvolution software and with our TAMI Molecule Identification software for the provision of elemental formula for further improved identification. 
3. Uniform compound independent response. EI and particularly Cold EI provide approximately uniform compound independent response hence the measured abundances correlate to their relative amount in the sample, with the exception of non-volatile and highly labile compounds. Thus, one can use the peak area percentage report in the data analysis procedure in order to obtain the relative abundance of any searched compound in its mixture. Heroin in its street drug powder is an example. 
4. Absence of ion suppression effects. In contrast to DART and/or DSA and/or DESI or all other types of ambient desorption ionization based real time analysis methods EI and/or Cold EI do not suffer from ion suppression effects that plague DART and DESI.  
5. Safe and low cost operation: The Open Probe fast GC-MS does not require any solvent like DESI and is thus safer to use for its operator. The vaporized sample is also fully contained at the Open Probe and fully swept forward. The Open Probe fast GC-MS helium requirement is 75 ml/min which is about 40-50 times lower than the helium consumption of typical DART.   
6. Ease of use and flexible sampling. Sampling into the Open Probe takes just a few simple steps hence simpler than in any other MS probe or ambient ionization device.  The Open Probe fast GC-MS is flexible in the use of various sample handing tools such as melting point vials as is or roughened with files, micro vials, swabs, silicone rubber tubes, SPME etc.  
7. The swab factor – Remote sample analysis capability: The Open Probe excels in the performance of full thermal desorption of all the samples on its sample holders (unlike DART, DESI or DSA). As a result, it is compatible with the use of swabs for remote sample collection. 
8. Sensitive Method and Device: The high sensitivity of electron ionization, full intra Open Probe thermal desorption, effective Open Probe self-cleaning and the fast response time of the Open Probe fast GC-MS result in improved sensitivity. Low femtogram range limit of detections were and can be achieved with it. 
9. Operation on your available lower cost GC-MS System: One of the most important benefits of the Open Probe fast GC-MS is that it is operated with the much lower cost quadrupole MS of standard Agilent GC-MS while the added separation serves as a lower cost alternative to costly high resolution MS (such as the Agilent 7200 QTOF which can be used if needed). 

We feel that the combination of these advantageous features makes the Open Probe fast GC-MS a novel and uniquely useful yet relatively low cost device for real time analysis with separation and mass spectrometry identification and quantitation. You are invited to ask us for more details and send us your samples for a demonstration of the technology.

  

References

1. Takats, Z.; Wiseman, J. M.; Gologan, B.; Cooks, R. G. Science 2004, 306, 471-473.
2. Cody, R. B.; Laramee, J. A.; Durst, H. D. Anal. Chem. 2005, 77, 2297-2302.
3. McEwen, C. N.; McKay, R. G.; Larsen, B. S. Anal. Chem. 2005, 77, 7826-7831.
4. Axion DSA (Direct Sample Analysis) System by PerkinElmer, Shelton CT USA. 
5. Chen, H.; Gamez, G.; Zenobi, R. J. Am. Soc. Mass. Spectrom. 2009, 20, 1947-1963.
6. Li, L. P.; Feng, B. S.; Yang, J. W.; Chang, C. L.; Bai, Y.; Liu, H. W. Analysts. 2013, 11, 3097-3103.     
7. Shahar, T.; Dagan, S.; Amirav, A. J. Am Soc. Mass. Spectrom. 1998, 9, 628-637.
8. Poliak, M.; Gordin, A.; Amirav, "Open Probe – A Novel Method and Device for Ultra Fast Electron Ionization Mass Spectrometry Analysis" A. Anal. Chem. 2010, 82, 5777-5782.
9. Amirav, A.; Gordin, A. "Open Probe Method and Device for Sample Introduction for Mass Spectrometry Analysis" Israel patent number 193003 (2011), USA patent 7928370 (2011) and Japan patent applications 2009-162366.  
10. Fialkov, A. B.; Morag, M. Amirav, A. "A Low Thermal Mass Fast Gas Chromatograph and its Implementation in Fast Gas Chromatography Mass Spectrometry with Supersonic Molecular Beams" A. J. Chromtogr. A. 2011, 1218, 9375-9383.
11. Amirav, A. and Fialkov. A. B. "Fast Gas Chromatograph Method and Device for Analyzing a Sample" US Patent # 8591630.  
12. Fialkov, A. B.; Steiner, U.; Jones, L.; Amirav, A. Int. J. Mass. Spectrom. 2006, 251, 47-58. 
13. Amirav, A.; Gordin, A.; Poliak, M.; Fialkov, A. B. J. Mass Spectrom. 2008, 43, 141-163.   
14. Alon, T.; Amirav, A. Rapid Commun. Mass Spectrom. 2006, 20, 2579-2588. 
15. Amirav, A.; Keshet, U.; Alon, T.; Fialkov, A. B. "Open Probe fast GC-MS - Real time analysis with separation" Int. J. Mass Spectrom. 2014, 371, 47-53.