Chemical analysis services available through Metitech
1: Selection or removal of single or multiple compounds from complex samples
The selective isolation platform was developed to create a fast-switching valve system, capable of automating chemical isolation based on measured retention times in two-dimensional gas chromatography. For example, after performing a comprehensive two-dimensional gas chromatographic (GCxGC) analysis on a complex sample, users can isolate specific chemicals or sets of chemicals from thousands of peaks for further research or testing. This innovative solution streamlines the process, making it easier to single out chemicals for applications such as structure elucidation, toxicology studies, or other tests of effect, offering a more efficient and cost-effective alternative to time-consuming synthesis methods.
With a single analysis, it’s possible to isolate quantities ranging from 10 to 100 ng, and through multiple analyses, up to the low-microgram range. The platform also supports selective enrichment of target chemicals within a matrix, broadening its range of applications.
The selective isolation process, illustrated in Figure 1, works as follows: from a comprehensive chromatogram of the sample, users can zoom in on a specific peak of interest (A). The peak is then selected, and the relevant retention times are automatically calculated (B). The switching valve is programmed to isolate the peak with precision (C), enabling highly targeted chemical analysis.
Key applications include:
- Environmental applications – unknown contaminants & exposure assessment
- Forensics – designer drug identification & exposure assessment
- Aroma profiling of single or multiple chemicals isolated directly from the sample
Figure 1: In this scenario, a selective isolation of a single chemical is performed. First, the chemical of interest is identified and selected (A). The system then automatically calculates the valve timing based on the retention times from both the first and second dimensions, along with the dead volume of the second column (B). Finally, the selective isolation of the chosen chemical is executed using this advanced method (C). On the resulting chromatogram, only the isolated peak will be visible, ensuring precise targeting of the desired compound.
The process of subtractive isolation, illustrated in Figure 2, allows for the selective removal of a single peak from a complex, comprehensive two-dimensional chromatogram. This is achieved by zooming in on the peak of interest (A), selecting it, and then automatically calculating the relevant retention times (B). The switching valve is then programmed to precisely isolate and remove the targeted peak (C).
This method is groundbreaking, as it enables the augmentation of a sample by removing specific compounds—something that was previously not possible. This approach is particularly valuable in evaluating aroma profiles, as it allows for the subtraction of chemicals to better link the chemical composition of a sample with our sensory perception of smell.
Key applications of subtractive isolation include:
- Food & Flavor: Enhancing aroma profiles by removing selected components.
- Cosmetics: Optimizing fragrance mixtures through targeted compound removal.
Figure 2: In the subtractive isolation scenario, a single chemical is selectively removed from the sample. First, the unwanted chemical is identified and selected (A). The system then automatically calculates the valve timing based on the retention times from both the first and second dimensions, as well as the dead volume of the second column. The valve is programmed with opposite positions compared to the selective isolation process (B). Finally, the subtractive isolation of the selected chemical is performed (C). In the resulting chromatogram, a “gap” or “hole” appears where the removed chemical was located.
The platform's schematic, shown in Figure 3, highlights the flow-modulated GCxGC system. After passing through the second column, the effluent enters a modified microfluidic switching device housed inside the GC oven. This device switches between the divert line and the isolation line. The isolation line is connected to a mass spectrometer, enabling spectral analysis of the isolated peaks. The isolation line is then transferred from the GC oven via a modified heated transfer line to a sorbent tube, cooled by a Peltier device. For specific applications, the first and second columns can be adjusted to achieve the most selective separations. The rest of the system is engineered with optimized capillary dimensions to ensure efficient switching speeds.
This technology is patented and published. Patent number: WO 2024/194405A1
Figure 3: The schematic of the single molecule isolation platform demonstrates the process: the sample inlet is connected to a flow-modulated GCxGC setup. The outlet of the second column (COLUMN II) feeds into a Deans switch, which facilitates selective or subtractive isolation of chemicals. The Deans switch has two outlets: one leading to an open capillary (Divert line), and the other transferring analytes to a passive splitter. This splitter divides the stream between the Q-TOF detector and the isolation line, which is connected to the isolation tube.
2: Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-TOF-MS)
Technology - Ionization
Proton Transfer Reaction Mass Spectrometry (PTR-MS) is a cutting-edge analytical technique designed for the real-time detection and quantification of trace levels of volatile organic compounds (VOCs) in gases, liquids, and solids. PTR-MS operates on the principle of proton transfer reactions, where ions are generated by transferring a proton from a reagent gas—typically H3O+, but other reagent ions like NH4+ or NO+ can also be used—to target analyte molecules. With this method, the sample is introduced into a reaction chamber, where it interacts with the supplied reagent gas (Figure 4). The resulting protonated ions are analyzed using a mass spectrometer, enabling the determination of their mass-to-charge ratios, which facilitates the identification and quantification of various VOCs based on their distinct mass spectra.
Figure 4: The schematic illustrates the types of reactions occurring within the PTR reaction tube. Selectable reactants are introduced to the ion source, and the ions are subsequently transferred into the reaction chamber, where they react with the samples—most commonly through proton transfer reactions. Depending on the chosen reactant, different reaction pathways can be explored, enhancing the selectivity and sensitivity of the application. An example of volatile measurement in breath samples is shown in the top right, demonstrating real-time quantitative results obtained using the PTR reaction.
Technology – Mass Spectrometry
The PTR-MS technique employs a time-of-flight mass analyzer, which achieves rapid data acquisition rates, providing a time resolution of one spectrum per second (Figure 5). Each recorded spectrum encompasses spectral information across the entire mass range examined, enabling non-targeted chemical analysis to be performed post-acquisition, even if the identities of the chemicals are initially unknown. This instrument boasts a mass resolution of up to 15,000, allowing for the assignment of elemental compositions to each detected ion. When combined with the robustness of the ion source against diverse humidity matrices, PTR-MS becomes a powerful tool for real-time analysis of volatile organic chemicals. Additionally, its portability enables deployment for field applications outside the laboratory.
Figure 5: The schematic depicts the operational principle of the time-of-flight mass spectrometer. Here, the mass-to-charge ratio (m/z) is proportional to the square of the flight time of each chemical (t²). Other parameters, such as voltage (U) and flight tube length (L), remain constant within a single experimental setup. Consequently, lighter ions travel faster through the flight tube than heavier ions.
Applications and literature
PTR-MS has a wide range of applications across various fields, including environmental monitoring, atmospheric chemistry, food and flavor analysis, medical research, and industrial process monitoring. Its real-time capabilities, high sensitivity, and ability to detect a broad spectrum of compounds make it an invaluable tool for understanding complex chemical processes and tracking trace substances in diverse environments. Key research areas and landmark publications are summarized in Figure 6.
Figure 6: Important papers published in the strategic application fields of PTR-MS.
3: Multidimensional Gas Chromatography/High-Resolution Mass Spectrometry and Associated Services
At our lab at the University of Pisa, we utilize a fully equipped comprehensive two-dimensional gas chromatograph (GCxGC) connected to a high-resolution time-of-flight mass spectrometer (HR-TOFMS). This platform is highly effective for the separation and identification of volatile organic compounds. In addition to standard GCxGC-HR-TOFMS analysis, we offer a wide range of options for sample extraction and preconcentration, allowing us to extract and enrich volatile compounds from various matrices, including water-based samples relevant to food, cosmetics, biomedical, and environmental applications.
This combination of advanced sample preparation techniques and the powerful separation capabilities of GCxGC provides a robust solution for both sample characterization and qualitative or non-targeted analysis. Moreover, our cutting-edge extension to the GCxGC system allows for the selective isolation of individual chemicals from complex samples, enabling targeted studies of their effects.
Services We Provide:
● A variety of sample preparation methods for diverse sample matrices, including:
◦ Solid Phase Microextraction (SPME)
◦ Thin Film Extraction (TFE)
◦ Sorptive Coated Stir Bar Extraction (SBSE)
◦ Thermal Extraction with Desorption (TD)
◦ Dynamic Headspace Extraction (DHS)
● A state-of-the-art platform for single molecule isolation, detailed earlier as a separate service.
● Multi-sample batch analyses and data processing, utilizing a top-down, data-driven approach.
● Consulting services in instrumental organic analytical chemistry.
Figure 7: The comprehensive two-dimensional GCxGC-Q-TOF system (left) with a multipurpose sample preparation platform (right) in our laboratory at the University of Pisa.
4: Consultant work in the field of instrumental organic analytical chemistry
With over 5 years of experience, I offer courses in both basic and advanced GC-MS and GCxGC-MS, covering theoretical principles and practical method development. Additionally, I regularly conduct training in GC-MS data analysis using MassHunter (qualitative, quantitative, single sample, and batch) as well as GCxGC data analysis with ChromaTOF or GC Image software.
