FIT was founded in 2015 to develop and commercialize a new generation of ionization sources and ion mobility systems to expand the applicability of mass spectrometry.
We are experts in SESI ionization. Since 2008, we have accumulated several years of experience in the development of industrial, security, and biomedical applications of SESI for research purposes. In 2014 and 2015, we joined the project ACID (Marie Curie) at ETH-Zurich and developed the Low Flow SESI source, which provided record ionization efficiency, enabling previously impossible studies. We have further improved performance and usability so as to bring SESI-MS analysis and breath analysis to the laboratory. Today, our goal is to improve these designs, further improve performances, and to provide better solutions that allow our customers to focus on the science.

The team

Aerospace engineers, biochemistry scientists, entrepreneurs and dreamers

Guillermo Vidal de Miguel
M. Eng. in  Aeronautical Engineering and PhD in Fluid Mechanics. He holds 12 patents in Secondary Electrospray Ionization, Transversal Modulation Ion Mobility coupled with Mass Spectrometry, and their related applications. GVM worked for the defense industry (Eurofighter program) before he joined the Mechanical Engineering group of Yale University (USA) to work on aerosol focusing lenses and electrospray thrusters. There, he learned about the pioneering work of P. M-Lozano, who was using an electrospray to ionize and analyze breath. GVM was then appointed Head of the R&D team at SEADM, where he developed SESI and Ion mobility systems for Explosives detection.
GVM has worked in close collaboration with Thermo Fisher Scientific R&D team on the development of a Transversal Modulation Ion Mobility Spectrometer with an Add-on architecture to enhance the separation capacity of commercial mass spectrometers. In 2014, he joined the Organic Chemistry Department at ETH-Z to better understand the perspectives of the scientists using analytical instruments and to work with P.M-Lozano on a SESI optimized for breath analysis. This was the seed of the SUPER SESI.

Miriam Macía Santiago
Eng. in Aeronautical Engineering. After completing her studies, MMS joined the Mechanical Engineering Group of Juan F. de la Mora at Yale University to assist in mechanical design and logistics. In her stage at SEADM, she gained experience in secondary electrospray ionization, and ion mobility (she holds two patents), being a key member of the team that developed the LF-SESI, and the different demonstrators of the new technology called Transversal Modulation Ion Mobility Spectrometry. During her stay in the Organic Chemistry Department at ETH-Z she also had the opportunity to better understand the vision of the users of the equipments that she helps to develop. She is in a constant search for improvement the functionality of the product and perfectioning the production processes, in order to achieve the best final quality.

Gabriel Jaumà Gómez
Junior Aerospace Engineer. GJG was selected by FIT to collaborate in the development of an adapted SUPER SESI that was optimized for Sciex’s Mass Spectrometers. With an impeccable academic record and having had early collaborations with the Mathematics and Applied Physics departments of the Technical University of Madrid, GJG rapidly became a key member of the team. GJG chose to work at FIT in his search of an opportunity to develop his skills and to do meaningful work with a positive impact on society.
GJG has contributed with valuable and fresh ideas that have helped to improve performances and to streamline production. He made his bachelor’s degree final thesis during his undergraduate stance at FIT, and gave an oral presentation at the VIII Congress of the Spanish Society for Mass Spectrometry. His professional trajectory has barely started, but his early achievements point to an outstanding future.

Technology and R&D

SESI, a short review of the development

Detecting the volatile organic compounds (VOCs) released by biological systems is useful because it enables non-invasive monitoring of the metabolic processes in real time.
However, detecting VOC’s is very challenging because they are released into the gas stream at very low concentrations. In particular, the more biologically relevant metabolites tend to be large molecules with very low vapor pressure. For this reason, the performances of the instruments used are crucial to detecting the metabolites that can be used to identify the different metabolic processes.

The problem addressed:
In order to detect the species of interest at minute concentrations, the system utilized must provide a very high sensitivity, which is defined as the minimum concentration of the analyte that produces a signal. For this, the ionization technique must provide a high ionization efficiency, defined as the ratio of ions transferred to the analyzer over molecules received by the analyzer.
High volatile species can be detected, even when they are present in very low concentrations, provided that the sensitivity of the VOC analyzer is good enough. For instance, in 2009, the concentration of ammonia, acetone, methanol, ethanol, and isoprene in human breath were measured using a Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) system [1]. In another study, 1,3-Butadiene was detected at a concentration of 9 ppt[2] in ambient air. This study also measured Toluene, Benzene, and Ethanol. Proton Transfer Reaction Mass Spectrometry (PTR-MS) has been used to detect VOCs at very low concentrations, providing limits of detection in the ppt range. With ppt sensitivity, and if sensitivity was the only limiting factor, one would expect to be able to detect very low volatility species, with vapor pressures in the range of 10-12 Bar. PTR-MS and SIFT-MS are very powerful to detect highly volatile species, but they struggle with less volatile ones. For instance, the less volatile species mentioned in the recent review on PTR-MS are Phenol and Aniline[3] (See Table 1 of the mentioned review). The vapor pressures of Aniline and Phenol are 5·10-4 Bar and 8·10-4 Bar, which are much higher than the theoretically expected limit of 10-12 Bar for a sensitivity in the ppt level. This mismatch of over seven orders of magnitude shows that the performances of PTR-MS and SIFT-MS are limited by other effects.
The goal of FIT's Secondary Electro-Spray Ionization Mass Spectrometry (SESI-MS) technology is to provide an analytical tool for the detection of low volatility species. SESI is a very novel technology. Different configurations have been proposed by various researchers, with diverse results. The underlying ionization mechanism is so powerful that the first configurations outperformed other technologies even though they were not optimized. Over the last years, the ionization efficiency has been improved dramatically, but other important effects hold the Limits of Detection (LoD). Currently, background levels and condensation effects are the limiting factors defining the LoD for low volatility species.
The development of SESI shows how these effects became more important as the ionization efficiency was improved and more metabolites could be detected. The following section of this document briefly summarizes the history of the development of SESI, from the first discoveries to the first commercial release, to illustrate the role of these effects and how they have been addressed in the consecutive developments. In September of 2016, the SUPER SESITM was the first commercial SESI source designed as a commercial product in compliance with the European Safety and Electromagnetic Compatibility regulations. This source was designed to optimize ionization efficiency, background levels, condensation effects, and usability.

Discovery:
The mechanism of SESI was discovered by Fenn et. al. in the development of the Electrospray[4],[5]. They found that very low concentration of contaminants in the gas were efficiently ionized by the cloud of ions formed with the electrospray, and hypothesized that this could be used to detect volatile species at trace levels.
In a first stage, several authors started to demonstrate the potential of SESI-MS in different applications. These authors used home-made non-optimized SESI sources. Some authors include: Wu, H. Hill et. al. used SESI to demonstrate its suitability for detecting vapor traces of illicit drugs [6]. Martinez Lozano showed that it could be used to detect volatiles of explosives[7], volatiles released by the human skin[8], and to analyze the content of trace metabolites in breath[9],[10], and J. Hill was able to characterize and differentiate bacterial cultures with SESI-MS[11].

Understanding:
The first attempt to develop an industrial SESI-MS analyzer aimed to create an explosive detector for rapid screening of air cargo containers. This industrial development fueled some of the first studies, which provided a better understanding of the mechanisms of ionization[12] , and the dynamics of the different species in the expanding electrospray plume[13].

Improving the ionization efficiency:
These studies showed that the ionization efficiency was limited by two factors: dilution of ions due to coulomb repulsion, and dilution of neutral molecules due to mixing with the clean gas used in the inlet of the analyzer, including carrier gasses and counterflow gasses. In order to minimize these effects, G. Vidal-de-Miguel et. al. invented and developed the Low Flow SESI configuration, which incorporated a metal plate that separated the ionization region and the inlet of the analyzer[14],[15]. The Low Flow SESI improved the ionization efficiency by a factor of 70 for trinitrotoluene, and it was integrated by the company SEADM in its explosive detectors to improve the overall Limits of Detection. In view of this improvement, a Low Flow SESI prototype was developed at ETH for its use in biological applications[16]. The Low Flow SESI improved the sensitivity, which in turn enabled an improvement on the Limits of Detection (LoD) for various applications, including breath analysis[17], plant metabolism analysis [18], etcetera.
However, the Low Flow SESI was very vulnerable to the accumulation of contaminants, which condensate in the ionizer. This produces high background signals, which deteriorate the LoD over time.
The Low Flow SESI design improved the ionization efficiency, but it has regions where low vapor pressure species tend to condensate, resulting in high background levels and memory effects. In addition, accessing the internal parts of the ionizer was difficult, and cleaning and maintenance procedures became very time-consuming. Paradoxically, the improved ionization efficiency also increased the background levels of the Low Flow SESI, especially for the lowest volatility species, which are usually more relevant from a biological standpoint.

Improving the Limits of Detection (LoD):
The Low Flow SESI configuration provided a proof of concept, but most importantly, it allowed the requirements of a SESI-MS system to be redefined. It was found that operational aspects like ease of use and maintenance were essential to provide a sustained optimum performance over time.
The goal of the next SESI generation was to remove the electrodes while maintaining a high ionization efficiency. For this, a new numerical tool was used to simulate the flow and electrostatic configuration of the ionization region. This method combines a finite element method in the bulk domain and an analytical solution at the tip of the spray to overcome numerical instability problems associated with the tip. Using this numerical method, the geometry was carefully designed to maintain a low turbulence configuration. The boundary layer that separates the sample gas and the clean gas is stable. As a result, dilution problems are minimized without adding any extra element, and in an open chamber with no stagnated regions.
The resulting design, named electrode-less SESI, reduced memory effects and background levels by eliminating stagnated regions, cold spots, and adsorption materials. The electrode-less SESI configuration[19] eliminates the electrodes used in the Low Flow configuration, but it maintains the high ionization efficiency. This result in improved limits of detection [20].

Commercial maturity, from prototype to commercial product:
FIT was founded in 2016 by G. Vidal to develop and commercialize SESI technology. During the previous developments, it was found that operational aspects like ease of use and maintenance were essential to in routine operation and application development.
SUPER SESI was the first product released by FIT. It was fully redesigned to ease operation and to ionize low volatility species, which usually are larger molecules with higher biological significance. SUPER SESI incorporates the electrode-less configuration, which provides high ionization efficiency with reduced background levels. It includes all systems and subsystems in one single unit so that it is plug and play. In addition, the ionization chamber is designed to facilitate cleaning, disassembling and assembling cycles. This is important because, over time, the less volatile species tend to accumulate and produce background signals. By allowing the user to seamlessly clean the system, the background signals can be dramatically reduced, thus improving LoD for larger molecules. Finally, SUPER SESI was the first ionizer designed in compliance with the Safety and Electromagnetic Compatibility regulations of the EU. This milestone marked the transition between the research prototype and the commercial product.

[1] Patrik Spanel and David Smith; Progress in SIFT-MS: breath analysis and other applications; Mass Spectrometry Reviews, 2011, 30, 236– 267;
[2] B. J. Prince, D. B. Milligan and M. J. McEwan; Application of selected ion flow tube mass spectrometry to real-time atmospheric monitoring; Rapid Commun. Mass Spectrom. 2010; 24: 1763–1769
[3] X. Zhan, J. Duan, and Y. Duan; Recent developments of proton-transfer reaction mass spectrometry (PTR-MS) and its applications in medical research; Mass Spectrometry Reviews, 2013, 32, 143–165
[4] Fenn J.B.; Whitehouse C.M.; et. al.; Electrospray ionization for mass-spectrometry of large biomolecules; Science 246 (4926): 64-71, 1989
[5] Fuerstenau S., Kiselev P. and Fenn J. B.; ESIMS in the Analysis of Trace Species in Gases; Proceedings of the 47th ASMS Conference on Mass Spectrometry; 1999, Dallas TX.
[6] Wu C., Siems W.F. and Hill H.H.Jr.; Secondary Electrospray Ionization Ion Mobility Spectrometry/Mass Spectrometry of Illicit Drugs.; Anal. Chem.2000, 72,396-403).
[7] Martínez-Lozano P., de la Mora J.; et al. ; Secondary Electrospray Ionization (SESI) of Ambient Vapors for Explosive Detection at Concentrations Below Parts Per Trillion; Journal of the American Society for Mass Spectrometry, 20 (2009) 287-294
[8] Martínez-Lozano, P.; Mass spectrometric study of cutaneous volatiles by secondary electrospray ionization; International Journal of Mass Spectrometry, Volume 282, Issue 3, 1 May 2009, Pages 128-132
[9] Martinez-Lozano P. and de la Mora J.; Detection of fatty acid vapors in human breath by atmospheric pressure ionization mass spectrometry; Analytical Chemistry, 2008, 80, 8210–8215
[10] Martínez-Lozano P., de la Mora J., Electrospray ionization of volatiles in breath; International Journal of Mass Spectrometry, 265 (2007) 68-72
[11] Bean H.D., Zhu J., Hill J.E., Characterizing bacterial volatiles using secondary electrospray ionization mass spectrometry (SESI-MS), Journal of Visualized Experiments (2011) e2664
[12] Martínez-Lozano Sinues P., Criado E. and Vidal-de-Miguel G.; Mechanistic study on the ionization of trace gases by an electrospray plume; International Journal of Mass Spectrometry (2011)
[13] Vidal-de-Miguel G., Herrero A.; Secondary Electro Spray Ionization of complex vapor mixtures. Theoretical and experimental approach; Journal of the American Society for Mass Spectrometry (2012)
[14] Vidal-de-Miguel G.; Ionizer for vapor analysis decoupling the ionization region from the analyzer", USPTO 8,217,342 B2, Jul. 10, 2012
[15] Vidal-de-Miguel G., Macía, M., Pinacho P., Blanco, J. Low-Sample Flow Secondary Electrospray Ionization: Improving Vapor Ionization Efficiency” Analytical Chemistry, (2012), 84 (20), pp 8475–8479.
[16] Barrios, C.; Vidal-de-Miguel, G.; Martínez-Lozano-Sinues, P. Numerical modeling and experimental validation of a universal secondary electrospray ionization source for mass spectrometric gas analysis in real-time, Sensors and Actuators B: Chemical, Volume 223, Pages 217-225, Feb 2016
[17] Gaugg, T. M.;.M.L. Sinues, P.; et. al. Expanding metabolite coverage of real-time breath analysis by coupling a universal secondary electrospray ionization source and high resolution mass spectrometry – a pilot study on tobacco smokers Journal of Breath Research, Vol. 10(1), 1-10; 2016
[18] Barrios-Collado, C.; García-Gomez, D.; Zenobi, R.; Ibañez, A.J.; Vidal-de-Miguel, G.; Martínez-Lozano-Sinues, P. Capturing in vivo plant m by real-time analysis of low to high molecular weight volatiles Analytical Chemistry, 2016 Feb 16;88(4):2406-12
[19] Vidal-de-Miguel, G.; Ion source for analysis of low volatility species in the gas phase, USPTO Patent Application No. 62424751; Nov. 2016.
[20] Vidal-de-Miguel G., Martinez-Lozano Sinues P.; Secondary Electrospray Ionization (SESI) for breath analysis, an engineering perspective of the technical development; IABR Breath Summit 2016 in Zurich, Switzerland.

Technology and R&D

Transversal Modulation Ion Mobility Spectrometry

Principle of operation:
TMIMS combines an axial and steady electric field and a transversal and oscillating field. When the time of residence of the ions within the TMIMS equates with the period of the oscillating fields, the ion trajectories are focused at the outlet of the device, and the ions are outputted. The system selects which mobility is transferred by setting the frequency of the oscillating field,

History of the development:
The first prototype (TMIMS-1) was coupled with an electrometer, and allowed us to prove the viability of the technology. The second prototype (TMIMS-2) incorporated two TMIMS stages in series, and showed how the TMIMS enables IMS-IMS prefiltration coupled with different mass spectrometers. The last prototype (TMIMS-L) uses a ladder of small stages. It was designed to meet all the requirements of the end user in an analytical chemistry laboratory. It is compatible with standard ion sources and mass spectrometers, and can be readily integrated within normal laboratory workflows.

IonMax/TMIMS-L/Orbitrap tests:
After successfully completing the development of the TMIMS-L in our lab, we demonstrated the system at the demo lab of Thermo Fisher Scientific in Bremen. The TMIMS-L was coupled with an Orbitrap, and we were able to easily obtain IMS-MS data for several samples with unprecedented accuracy. This was a very important milestone for us, we are now fully committed to develop and provide a reliable IMS solution for Orbitrap users.

Applications:
Ideal for ESI-IMS-MS. Its contunious output greatly facilitates the integration with FT-MS instruments that require a flexible MS scan rate or a flexible IMS scanning strategy.

  • Collisional Cross Section (CCS) and conformational states of proteins:
  • Isomers separation:
  • Monitorization of gas-phase dopant-induced conformational changes:

Publications

Thomas Gaugg, M.; García-Gomez, D.; Barrios-Collado, C.; Vidal-de-Miguel, G.; Vidal-de-Miguel, G.; Zenobi, R.; Martínez-Lozano-Sinues, P. Expanding metabolite coverage of real-time breath analysis by coupling a universal secondary electrospray ionization source and high resolution mass spectrometry – a pilot study on tobacco smokers  Journal of Breath Research, DOI: 10.1088/1752-7155/10/1/016010, February 2016

Barrios-Collado, C.; García-Gomez, D.; Zenobi, R.; Ibañez, A.J.; Vidal-de-Miguel, G.; Martínez-Lozano-Sinues, P. Capturing in Vivo Plant Metabolism by Real-Time Analysis of Low to High Molecular Weight Volatiles Analytical Chemistry, DOI: 10.1021/acs.analchem.5b04452, January 2016

Meyer, N. A.; Root, K.; Zenobi, R.; Vidal-de-Miguel, G. Gas-Phase Dopant-Induced Conformational Changes Monitored with Transversal Modulation Ion Mobility Spectrometry Analytical Chemistry, DOI: 10.1021/acs.analchem.5b0750, January 2016

García-Gómez, D.; Gaisl, T.; Barrios-Collado, C.; Vidal-de-Miguel, G.; c; Zenobi, R. Real-Time Chemical Analysis of E-Cigarette Aerosols By Means Of Secondary Electrospray Ionization Mass Spectrometry   Chemistry – A European Journal, DOI: 10.1002/chem.201504450, January 2016

Barrios-Collado, C.; Vidal-de-Miguel, G.; Martínez-Lozano-Sinues, P. Numerical modeling and experimental validation of a universal secondary electrospray ionization source for mass spectrometric gas analysis in real-time  Sensors and Actuators B: Chemical, Volume 223, Pages 217-225, September 2015

García-Gómez, D.; Bregy, L.; Barrios-Collado, C.; Vidal-de-Miguel, G.; Zenobi, R. Real-time high-resolution tandem mass spectrometry identifies furan derivatives in exhaled breath  Analytical Chemistry; vol. 87 (13), pp 6919–6924; June 2015

García-Gómez, D.; Martínez-Lozano, P.; Barrios-Collado, C.; Vidal-de-Miguel, G.; Gaugg, M.; Zenobi, R. Identification of 2-Alkenals, 4-Hydroxy-2-alkenals, and 4-Hydroxy-2,6-alkadienals in exhaled breath condensate by UHPLC-HRMS and in breath by real-time HRMS  Analytical Chemistry, Volume 87, Pages 3087-3093, February 2015

Vidal-de-Miguel, G.; Macía, M.; Barrios, C.; Cuevas, J. Transversal Modulation Ion Mobility coupled with Mass Spectrometry: Exploring the IMS-IMS-MS Possibilities of the Instrument   Analítical Chemistry; Anal. Volume 87, pp 1925–1932; January 2015

Barrios-Collado, C.; Vidal-de-Miguel, G. Numerical algorithm for the accurate evaluation of ion beams in transversal modulation ion mobility spectrometry: Understanding realistic geometries  International Journal of Mass Spectrometry, Volume 376, Pages 97–105, December 2014

Rodriguez-Lujan, I.; Bailador, G.; Sanchez-Avila, C.; Herrero, A.; Vidal-de-Miguel, G. Analysis of pattern recognition and dimensionality reduction techniques for odor biometrics  Knowledge-Based Systems, DOI: 10.1016/j.knosys.2013.08.002, November 2013

Vidal-de-Miguel, G.; Macía, M.; Pinacho, P.; Blanco, J. Low Sample Flow Secondary Electro-Spray Ionization, improving vapor ionization efficiency  Anal. Chem.; DOI: 10.1021/ac3005378; September 12, 2012

Vidal-de-Miguel, G.; Macía, M; Cuevas, J. Transversal Modulation Ion Mobility Spectrometry (TM-IMS), a new mobility filter overcoming turbulence related limitations  Anal. Chem.; DOI: 10.1021/ac301127u; August 2012

Attoui, M.; Fernandez-Garcia, J.; Cuevas, J.;Vidal-de-Miguel, G.;Fernández de la Mora, J. Charge evaporation from nanometer polystyrene aerosols  Journal of Aerosol Science, Volume 55 (Jan 2013), Pages 149–156, August 2012

G. Vidal-de-Miguel, J. Fernandez de la Mora. Continuously Converging Multistage Focusing Lenses to Concentrate Aerosols at High Reynolds Numbers  Aerosol Science and Technology Volume 46, Issue 3, August 2012

Vidal-de-Miguel, G.; Herrero, A. Secondary Electrospray Ionization of Complex Vapor Mixtures. Theoretical and Experimental Approach  Journal of the American Society for Mass Spectrometry; Volume 23, Number 6 (2012), 1085-1096, February 2012

Martinez-Lozano, P.; Criado-Hidalgo E.; Vidal-de-Miguel, G.; Cristoni, S.; Franzoso, F.; Piatti, M.; Brambilla,P. Differential mobility analysis-mass spectrometry coupled to XCMS algorithm as a novel analytical platform for metabolic profiling  Metabolomics, Vol 7, num 2, June 2011

P. Martinez-Lozano, Ernesto Criado, Guillermo Vidal-de-Miguel Mechanistic study on the ionization of trace gases by an electrospray plume   International Journal of Mass Spectrometry, December 2011

Patents

Vidal de Miguel, “Transversal Modulation Ion Mobility Spectrometer with reduced voltage and improved robustness and resolving power”, USPTO 62/114,601; Feb. 11, 2015. Patent application.

Vidal de Miguel, “Method and apparatus to generate beams of ions with controlled ranges of mobilities”, USPTO 62/077,412; Nov. 10, 2015. Patent application.

G. Vidal de Miguel, “Ionizer for vapor analysis decoupling the ionization region from the analyzer”,USPTO 8,461,523 B2, Jun. 11, 2013. Granted.

Vidal de Miguel, J. Fernandez de la Mora, “Method and apparatus to sharply focus aerosol particles at high flow rates and over a wide range of sizes”, USPTO 8,247,764 B2, Aug 21, 2012. Granted.

G. Vidal de Miguel, “Ionizer for vapor analysis decoupling the ionization region from the analyzer”, USPTO 8,217,342 B2, Jul. 10, 2012. Granted.

G. Vidal de Miguel, D. Zamora, M. Amo, A. Casado, G. Fernandez de la Mora, J. Fernandez de la Mora, “Method for detecting atmospheric vapors at parts per quadrillion (PPQ) concentrations”, EP2538208 A1, Jun. 25, 2012. Pending.

Borrajo Peláez, E. Criado Hidalgo, G. Vidal de Miguel, “Method and apparatus for monitoring stress levels or sudden changes of humor in humans or other individuals in real time”, 13/161,662 (USPTO), Jun. 16, 2011. Pending.

In the media