Direct coupling of Solid Phase Microextraction to Mass Spectrometry: via liquid desorption

The direct coupling of SPME with Mass Spectrometry (MS) analyzers has been investigated for more than 20 years. In fact, different strategies have been developed by several groups worldwide and most have been appropriately reviewed by Fang et al¹ and  Deng et al². Given the wide diversity of SPME-MS couplings, it is difficult to categorize them based on one well-defined characteristic. Following a similar approach to the one suggested by Venter et al³, one could classify SPME-MS couplings according to the desorption mechanism: solvent^4,5, thermal^6,7 or laser desorption⁸. Herein, I present a brief summary of the most recent developments on SPME-MS techniques that utilize liquid desorption. Essentially, this field can be divided in three sub-categories: direct-desorption from the extraction substrate^9–11, desorption into an elution chamber¹², or desorption into a smaller compartment with efficient ionization (nano-electrospray emitter)^5,13. As the first category is particularly novel and it presents a wide-range of exciting applications, I will leave this topic for an upcoming contribution to µextraction technologies.

To the best of my knowledge, the first interface of SPME to MS via liquid desorption was done by Möder et al. (Germany, 1997)¹⁴ through a desorption chamber similar to the one designed by Chen and Pawliszyn in 1995¹⁵. Since then, multiple improvements to the desorption chamber have been performed as to decrease the volume of the elution/ionization solvent, which aims to improve sensitivity^16–18. Some of these approaches are less practical than others, however most have managed to obtain the required limits of quantitation for the selected application. Approximately one year ago, we published a manuscript in Analytical Chemistry entitled “Biocompatible Solid-Phase Microextraction Nanoelectrospray Ionization: An Unexploited Tool in Bioanalysis”⁵ (open access). In this work we built upon the approach initially proposed by Walles et al. in 2005¹³ where SPME was coupled to MS via nano-ESI emitters. Essentially, the molar enrichment factor offered by biocompatible-SPME (BioSPME) fibres was fully utilized by eluting the analytes in ultra-small desorption volumes (V_des ≤ 4 μL). This resulted in remarkable limits of quantitation, and satisfactory figures of merit were attained for all the analytes tested (drugs of abuse and therapeutic drugs) in different matrices (urine and blood) with exceedingly short sample preparation times (t ≤ 2 min). I think the greatest impact that BioSPME-nanoESI will have

BioSPME-nanoESI

in bioanalytical applications has yet to come. Certainly, this technology could be used as a complementary tool to LC-HRMS towards the characterization of unknown compounds extracted from complex matrices such as tissue. Why? In essence, nanoESI not only yields higher ionization efficiency when compare to ESI¹⁹, but also allows for longer electrospray events that permit a far greater number of MS and MSⁿ experiments. Certainly, this unique feature of nanoESI is tremendously convenient in the identification of potential biomarkers extracted by SPME from precious samples!

Aware of the limitations that could thwart the high-throughput implementation of SPME-nanoESI such the high cost per analysis (due to the non-reusability of the emitters), as well as the difficulties associated with automatization of the process, we started exploring novel and cheaper alternatives. Hence, in a great collaboration with our colleagues from SCIEX, we recently assessed the open port probe (OPP) sampling interface developed by Van Berkel et al. at Oak Ridge National Laboratory.²⁰ Our findings showed that the OPP is a robust, sensitive, and ready-to-use interface for the direct coupling of Bio-SPME fibers to

BioSPME-OPP

mass spectrometry⁴. The OPP, as its name implies, is an interface exposed to the ambient air that has a continuous flowing stream where the SPME fibres can be easily inserted for elution of the enriched analytes. The greatest advantage of the OPP interface, when compared to other direct couplings to MS^7,12, is that it requires no modifications to the conventional ionization source setup employed by most labs, allowing the switch between LC-MS and OPP-MS to be achieved in a snap. Furthermore, OPP is suitable for high-throughput analysis (preparation times as low as 15 seconds per sample based on the 96-well plate format), offers high sensitivity (sub-ng mL^-1), and cost per analysis is low (reusable source with negligible carry over). All these features can be found in a manuscript recently published in Analytical Chemistry entitled “Open Port Probe Sampling Interface for the Direct Coupling of Bio-compatible Solid-Phase Microextraction to Atmospheric Pressure Ionization Mass Spectrometry”⁴. In that work we also explored in-line technologies such as multiple reaction monitoring with multistage fragmentation (MRM³) and differential mobility spectrometry (DMS) as to enhance the selectivity of the method without compromising analysis speed. Unquestionably, BioSPME-OPP coupling has great potential in bioanalytical laboratories for fast determination of therapeutic drugs and prohibited-substances in complex matrices. In my opinion, our advances on BioSPME-OPP are moving the implementation of SPME in the surgery room a bunch of steps forward.  

References

(1)     Fang, L.; Deng, J.; Yang, Y.; Wang, X.; Chen, B.; Liu, H.; Zhou, H.; Ouyang, G.; Luan, T. TrAC Trends Anal. Chem. 2016, 85, 61–72.

(2)     Deng, J.; Yang, Y.; Wang, X.; Luan, T. TrAC Trends Anal. Chem. 2014, 55, 55–67.

(3)    Venter, A. R.; Douglass, K. A.; Shelley, J. T.; Hasman, G.; Honarvar, E. Anal. Chem. 2014, 86 (1), 233–249.

(4)    Gómez-Ríos, G. A.; Liu, C.; Tascon, M.; Reyes-Garcés, N.; Arnold, D. W.; Covey, T. R.; Pawliszyn, J. Anal. Chem. 2017, acs.analchem.6b04737.

(5)     Gómez-Ríos, G. A.; Reyes-Garcés, N.; Bojko, B.; Pawliszyn, J. Anal. Chem. 2016, 88 (2), 1259–1265.

(6)     Gómez-Ríos, G. A.; Pawliszyn, J. Chem. Commun. 2014, 50 (85), 12937–12940.

(7)     Mirabelli, M. F.; Wolf, J.-C.; Zenobi, R. Anal. Chem. 2016, 88 (14), 7252–7258.

(8)     Wang, Y.; Schneider, B. B.; Covey, T. R.; Pawliszyn, J. Anal. Chem. 2005, 77 (24), 8095–8101.

(9)     Kuo, C. P.; Shiea, J. Anal. Chem. 1999, 71 (19), 4413–4417.

(10)   Deng, J.; Yang, Y.; Fang, L.; Lin, L.; Zhou, H.; Luan, T. Anal. Chem. 2014, 86 (22), 11159–11166.

(11)   Gómez-Ríos, G. A.; Pawliszyn, J. Angew. Chemie 2014, 53 (52), 14503–14507.

(12)   Ahmad, S.; Tucker, M.; Spooner, N.; Murnane, D.; Gerhard, U. Anal. Chem. 2015, 87 (1), 754–759.

(13)   Walles, M.; Gu, Y.; Dartiguenave, C.; Musteata, F. M.; Waldron, K.; Lubda, D.; Pawliszyn, J. J. Chromatogr. A 2005, 1067 (1–2), 197–205.

(14)   Möder, M.; Löster, H.; Herzschuh, R.; Popp, P. J. Mass Spectrom. 1997, 32 (11), 1195–1204.

(15)   Chen, J.; Pawliszyn, J. B. Anal. Chem. 1995, 67 (15), 2530–2533.

(16)   Lord, H. L. J. Chromatogr. A 2007, 1152 (1–2), 2–13.

(17)   van Hout, M. W. J.; Jas, V.; Niederländer, H. A. G.; de Zeeuw, R. A.; de Jong, G. J. Analyst 2002, 127 (3), 355–359.

(18)   McCooeye, M. A.; Mester, Z.; Ells, B.; Barnett, D. A.; Purves, R. W.; Guevremont, R. Anal. Chem. 2002, 74 (13), 3071–3075.

(19)   Needham, S. R.; Valaskovic, G. A. Bioanalysis 2015, 7 (9), 1061–1064.

(20)   Van Berkel, G. J.; Kertesz, V. Rapid Commun. Mass Spectrom. 2015, 29 (19), 1749–1756.

About the author

German Augusto Gómez-Ríos is a fourth year PhD candidate working at University of Waterloo under the supervision of Prof. Janusz Pawliszyn. German’s research focuses on the development of rapid diagnostic tools suitable for personalized medicine. These technologies are based on the direct coupling of Solid Phase Micro Extraction (SPME) devices to mass spectrometry instruments using different ionization techniques such as Direct Analysis in Real Time (DART), Desorption Electro Spray Ionization (DESI), nano-Electro Spray Ionization (nano-ESI), Open Port Probe (OPP), and Coated Blade Spray (CBS). In essence, German’s PhD thesis is mainly focused on the development, optimization and evaluation of diverse SPME-MS couplings that allow performing accurate, fast, and low-cost assays in different complex matrices. The ultimate goal of his research is to develop technologies that rapidly adapted by medical doctors and surgeons to individualize patient’s treatment.

You can follow him at twitter and Linkedin. In addition, you can browse his publications at Researchgate and Google scholar