The IVDr Platform Concept and Enabling Tools M.Spraul, H.Schfer, - PowerPoint PPT Presentation

The IVDr Platform Concept and Enabling Tools M.Spraul, H.Schäfer, C.Cannet, F.Fang Bruker BioSpin Biobank Webinar 2018

The IVDr Concept IVDr= In Vitro Diagnostic Research IVDr: Offering a completely standardized push button concept based on the IVDr Platform and its embedded solutions for Clinical and Translational Research allowing: - integration of results from different user groups all over the world, forming a sofar unthinkable reservoir of completely compatible spectral data and analysis results - Speed up translation to future diagnostic methods, be it for personalized medicine or populationwide studies on phenotypes and associated risk factors. - Development of future diagnostic routines with unmatched specificity and sensitivity - Enabling tools for quantification of a large number of compounds Ready to integrate LC-MS/MRMS into a Metabolic Profiler 2

The World of standardized Metabolomics NMR (SOP and fieldstrength) for the IVDr multi-solution platform allowing worldwide interdisciplinary exchange Foodomics Pharma Phenome Food Industry Metabolite ID Centers Clinical Pharma Phenome Toxicity Centers Screening Pharma Biobank Dose/response Qality optimization control Human Metab Clinical Research Service Universities Providers Hospitals, Environment Forensic Large medical and human practises health Departments 3

IVDr-Platform and Standardization : Allows to combine solutions, developed by Bruker BioSpin and/or external partners External Partner 1 External Partner 2 External Partner 3 External developments in Cardiovascular Prostate Cancer in Obesity/Diabetes Diseases progress Metabolic Syndrome R&D Ecosystem In progress In progress The IVDr Platform concept IVDr-Platform+Tools 4

Operation based on complete standardization guarantees unrestricted exchangeability of data worldwide • FoodScreener Data Analysis e.g. Addressing CVD risk worldwide Note: Epidemiological spectral databases only make sense, when data implemented are run identically ( SOPs ) Currently > 60 groups worldwide operate under Bruker NMR SOPs 5

Enabling Tools on the IVDr Platform for automatic analysis in Plasma/Serum B.I.LISA and B.I.LISA and B.I.BiobankTool (QC) B.I.QUANT-PS B.I.QUANT-PS B.I.QUANT-PS Fast version ~8 min Standard version ~ 18 min B.I.LISA One 1D-experiment 2*1D-experiments + 2D-J-Resolved Complete Package IVDr-Methods SOPs for plasma and serum 6

Improve your value proposition: Add B.I.QUANT-PS for every Plasma/Serum sample (Bruker IVDr Quantification in Plasma/Serum) Allows content stacking with Urine Quantification Biobanks Food related changes in Epidemiology Plasma/Serum Composition Output of B.I.QUANT-PS consists of 26 parameters show influence listing the concentrations on health for Plasma/Serum in detail. Such analysis supports research and produces Frequent health Ability to monitor invaluable input in: problems like and optimize cardiovascular treatment diseases, diabetes and cancer Information about personalized profile in plasma/serum B.I.LISA TM

Small molecule Quantification in Plasma/Serum B.I.QUANT-PS • 26 small molecules quantified • From same measurement as B.I.LISA (lipoprotein subclass analysis) 2 Viewpoints into disease! • Validated by DIN ISO Spiking • Retrospective analysis 8

Plasma/Serum Quantification in detail Example Creatinine 95% range In model set Actual Sample Outlier in Pyruvic Acid 9

Metabolite recognition and quantification under full automation Push button automation From measurement to final report. Shown are examples for the automatic Fit 1 0

TMAO quantification in plasma/serum Trimethylamine-N-oxide (TMAO) produced by gut microbiota metabolism of • dietary choline and carnitine has been shown to be associated with increased risk of cardiovascular disease (CVD) and to provide incremental clinical prognostic utility beyond traditional risk factors for assessing a patient's CVD risk. Clin Biochem. 2017 Nov;50(16-17):947-955. doi: 10.1016/j.clinbiochem.2017.06.003. Epub 2017 Jun 15. increased fasting serum TMAO levels associate with increased cIMT (carotid • intima-media thickness), independently of established cardiovascular risk markers, including insulin resistance, visceral obesity and fatty liver. Furthermore, the decrease of cIMT during a lifestyle intervention appears to be related to the decrease of TMAO levels. Sci. Rep. 6, 26745; doi: 10.1038/srep26745 (2016) 11

Lipoprotein Subclass Analysis B.I.LISA TM in health/disease related research Food/environment and health Diabetes type 2, obesity, metabolic syndrome High blood pressure Fatty Liver disease Stroke B.I.LISA supports research Alzheimer and produces invaluable Thrombosis (APO-A1 binds input in: Amyloids) Inflammatory Diseases Atherosclerosis Cancer (e.g. via blood Cerebrovascular General Cardiovascular triglycerides) Diseases diseases ( in prevention, early detection and treatment) B.I.LISA TM 12

Automatic report Lipoprotein Subclass Analysis Plasma/Serum (RUO only) 114 parameters in one experiment 13

Recognize cardiovascular risks in time to prevent incidents Donor had cardiovascular event 3 days after blood collection Control sample 14

Longitudinal NMR Reproducibility ringtest on 11 IVDr platforms in 5 organizations on lipoprotein analysis NCEP Criteria for Lipid and Lipoprotein Testing Instrument specific variance in QC samples 15 Innovation with Integrity

Improve your value proposition: Add B.I.QUANT-UR TM for every urine sample Bruker IVDr Quantification in urine. Can be combined with B.I.LISA TM on the same platform Biobanks Food related changes in urine Epidemiology metabolite Composition show The output of B.I.QUANT- UR TM consists of up to 150 influence on health parameters describing the metabolite composition in urine in detail. Such analysis supports Frequent health Ability to monitor research and produces problems like in invaluable input in: and optimize diabetes, metabolic treatment syndrom, kidney and cancer Information about personalized profile in urine B.I.Quant-UR TM

Urine Quantification B.I.QUANT-UR TM Report Excerpts basic Fully automatic 50 Metabolites Most often found : Based on B.I.Methods extended Report is ready 150 metabolites Few minutes after Basic + Measurement Disease markers : (PDF or XML) Also available Exceeds Neonate Extended ISO 17025 150 metabolites Requirements Wet and numerical 2 age ranges Spiking done on Better accuracy all metabolites for LOD estimation concentration Ranges given B.I.Quant-UR TM 17 .

Biobanks and NMR Gain new funding possibilities Extensive QC of Incoming samples Support development Of new diagnostic routines Sort out Aliquots with Low quality Build compatible Spectra base with NMR can provide added Phenome centers value to biobanks: QC process Generates NMR Data for storage Build compatible in the biobank spectra inventory To other biobanks ww Add Analysis Support Clinical trials Results to spectra with spectra instead And metadata: e.g. of aliquots to Offer metadata Urine Quant. Lipoprotein measure Subclass Analysis Selected spectra from inventory NMR for Biobanks 18

Biobank Workflow B.I.Methods – Spectrum – B.I.BioBankTool – QC results B.I.Methods B.I. BioBank Tool

Biobank QC in Plasma/Serum and Urine Criteria Plasma/Serum Criteria Urine Matrix Identity Test Matrix Identity Test Matrix Integrity Test Matrix Integrity Test Matrix Contamination Test Matrix ContaminationTest NMR preparation NMR preparation NMR measurement NMR measurement Medication Test Protein Background Test Test for further indicative parameters

Thank you M.Nauck et al Greifswald University Hospital • F.Trefz, J.Okun, G.Hofmann Heidelberg Hospital Pediatrics • J.Nicholson, J.Lindon, E.Holmes Imperial College London • A.Deelder, A.Meissner LUMC Leiden • C.Luchinat et al CERM Florence Italy • T.Bathen NMR Centre Trondheim • 21