Page 20 - Shimadzu Journal vol.9 Issue1

Clinical Research

Towards fast, routine blood sample

quality evaluation by Probe Electrospray

Ionization (PESI) metabolomics

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4*
Natalie Bordag 1,2,3# , Elmar Zügner , Pablo López-García 1,5* , Selina Kofler , Martina Tomberger , Abdullah Al-Baghdadi ,
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Jessica Schweiger , Yasemin Erdem , Christoph Magnes , Saiki Hidekazu , Wolfgang Wadsak , Hiroki Nakajima , Barbara Prietl 1,6
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CBmed GmbH, Center for Biomarker Research in Medicine, Graz, Austria. Medical University of Graz, Department of Internal Medicine, Division of
2 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria. Endocrinology and Diabetology, Graz, Austria.
3 Medical University of Graz, Department of Dermatology and Venereology, 7 Shimadzu Corporation, Kyoto, Japan.
Graz, Austria. 8 Medical University of Vienna. Department of Biomedical Imaging and
4 Joanneum Research Forschungsgesellschaft mbH, Health Institute for Biomedi- Image-guided Therapy, Division of Nuclear Medicine.
cine and Health Sciences, Graz, Austria. # correspondence should be addressed to NB natalie@bordag.com
5 Medical University of Graz, Institute for Medical Informatics, Statistics and *contributed equally
Documentation, Graz, Austria.
Abstract The unique advantages of PESI-MS to deliver full MS Keyword PESI, Probe electro spray ionization, minimal sample
spectra within minutes at ambient conditions enables routine, high- amount, sample quality control, method development, metabolomics
throughput applications. A still unresolved obstacle is that pre-analytical
sample handling strongly impacts the samples composition. In health
care and research, pre-analytical errors often remain undetected and
Introduction
disrupt diagnosis, treatment, clinical studies and biomarker validations
incurring high costs. This proof-of-principle study investigates the
suitability of PESI-MS for robust, routine sample quality evaluation. Mass-spectrometry (MS) is a sensitive, valuable analytical tool in
Here, human blood (n=50) was processed immediately or with a
many different fields and substantially advanced metabolomics.
time delay of 3 h to simulate the most common pre-analytical issue of
transportation time from beside to laboratory. The sample preparation Metabolomics is defined by measuring small molecules (<2000
method was developed to deliver ready-to-measure extracts in <8 min. Da) which reflect the biological phenotype and allow mechanistic
PESI-MS spectra were measured in both ionization modes in 2 min from
insights, identification of new therapeutic targets or development
as little as 2 µl plasma allowing 3 replicate measurements. The mass
spectra delivered 1200 stable features covering a broad chemical space of diagnostic biomarkers. Typically, MS-based metabolomics relies
with major metabolic classes (e.g. fatty acids, lysolipids, lipids). The time on liquid or gas chromatography coupled to high resolution mass
delay of 3 h was well predictable from 18 features with AUC > 0.95 with
spectrometers to increase specificity, sensitivity and chemical cov-
various machine learning and was robust against loss of single features.
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Our results serve as first proof for the unique advantages of PESI-MS erage . Such high-quality metabolomics set ups need extensive
in sample quality assessments. The results pave the way towards a expert knowledge, have long measurement times, produce large
fully automated, cost-efficient, user-friendly, robust and fast quality
amounts of data, require complicated analyses for successful re-
assessment of human blood samples from minimal sample amounts.
search and can struggle with large sample numbers . 2
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