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Clinical Research









            invalidating single features would not impede a sample quality de-  5.  Sakamoto, K.  et al. Ambient mass spectrometry-based detection
            termination based on a multi-feature read-out.        system for tumor cells in human blood. Transl. Cancer Res. 7, 758–
                                                                  764; DOI:10.21037/tcr.2018.04.20 (2018).
               Our aim was to determine whether PESI-MS has the potential
                                                               6.  Saha, S., Mandal, M. K. & Hiraoka, K. Direct detection of trace level
            to determine sample quality, for which one pre-analytical issue was
                                                                  illicit drugs in human body fluids by probe electrospray ionization
            used as proof-of-principle. Our results demonstrate that PESI-MS
                                                                  mass  spectrometry  (PESI-MS).  Anal. Methods  5, 4731–4738;
            spectra contain multiple robust biomarkers. Additionally, many   DOI:10.1039/c3ay41117f (2013).
            other stable features were detected which renders detection of
                                                               7.  Hainaut, P., Vaught, J., Zatloukal, K. & Pasterk, M. Biobanking of
            robust biomarker for other pre-analytical highly likely.  human biospecimens: Principles and practice.  Biobanking Hum.
                                                                  Biospecimens Princ. Pract. 1–239; DOI:10.1007/978-3-319-55120-3
                                                                  (2017).

                            Conclusions                        8.  Kamlage, B. et al. Quality Markers Addressing Preanalytical Variations
                                                                  of Blood and Plasma Processing Identified by Broad and Targeted
                                                                  Metabolite Profiling.  Clin. Chem.  60, 399–412; DOI:10.1373/
            Our results provide a proof-of-concept that PESI-MS is a prom-  clinchem.2013.211979 (2014).
            ising technology for fast and comprehensive quality control of
                                                               9.  Lippi, G. et al. Quality standards for sample collection in coagulation
            blood samples.                                        testing. Semin. Thromb. Hemost. 38, 565–75; DOI:10.1055/s-0032-
               The single-step MeOH precipitation delivered ready-to-measure    1315961 (2012).
            extracts in <8 min when manually performed and could be consid-  10. Kamlage,  B.  et  al.  Impact  of  Prolonged  Blood  Incubation  and
            erably speed-up with filtration and automatization. As little as 2 µl   Extended Serum Storage at Room Temperature on the Human
                                                                  Serum  Metabolome.  Metabolites  8,  6; DOI:10.3390/metabo
            plasma sufficed for PESI-MS spectra in both ionization modes in
                                                                  8010006 (2018).
            2 min with 1200 stable features covering a broad chemical space.
                                                               11. Wagner-Golbs, A. et al. Effects of Long-Term Storage at −80 °C on
            The time delay of 3 h was well predictable with five common
                                                                  the Human Plasma Metabolome. Metabolites 9, 99; DOI:10.3390/
            machine learning approaches based on 18 selected features with
                                                                  metabo9050099 (2019).
            an excellent AUC > 0.95 and was robust against failure of single
                                                               12. Yin, P. et al. Preanalytical aspects and sample quality assessment in
            features. Although for a future high-throughput application more   metabolomics studies of human blood.  Clin. Chem.  59, 833–45;
            optimization, reduction of noise and automatization are needed,   DOI:10.1373/clinchem.2012.199257 (2013).
            our results demonstrate the unique advantages of PESI-MS. The   13. Lehmann, R. Preanalytics: what can metabolomics learn from clinical
            results pave the way towards a fully automated, cost-efficient, user-   chemistry? Bioanalysis 7, 927–930; DOI:10.4155/bio.15.23 (2015).
            friendly, robust and fast quality assessment of human blood sam-  14. Ghini, V., Quaglio, D., Luchinat, C. & Turano, P. NMR for sample
            ples from minimal sample amounts.                     quality assessment in metabolomics.  N. Biotechnol.  52, 25–34;
                                                                  DOI:10.1016/j.nbt.2019.04.004 (2019).
                                                               15. Bordag, N. et al. Towards fast, routine blood sample quality evalua-
                                                                  tion by Probe Electrospray Ionization (PESI) metabolomics. medRxiv
                                                                  2021.04.18.21254782; DOI:10.1101/2021.04.18.21254782 (2021).
            References
            1.  Sands, C. J. et al. Representing the Metabolome with High Fidelity:   16. Lampen, P., Hillig, H., Davies, A. N. & Linscheid, M. JCAMP-
               Range and Response as Quality Control Factors in LC-MS-Based   DX  for Mass  Spectrometry.  Appl. Spectrosc.; DOI:10.1366/
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                                                               17. R Core Team. R: A language and environment for statistical comput-
            2.  Segers, K., Declerck, S., Mangelings, D., Heyden, Y. Vander &   ing. R Foundation for Statistical Computing.(2020).
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            3.  Hiraoka, K., Nishidate, K., Mori, K., Asakawa, D. & Suzuki, S.
               Development of probe electrospray using a solid needle.  Rapid
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               DOI:10.5702/massspectrometry.A0092 (2020).





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