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

M.Spraul, H.Schäfer, C.Cannet, F.Fang Bruker BioSpin Biobank Webinar 2018

The IVDr Platform Concept and Enabling Tools

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

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3 Phenome Centers Clinical Phenome Centers Biobank Qality control Pharma Metabolite ID Pharma Toxicity Screening

Pharma Dose/response

• ptimization

Clinical Service Providers

Hospitals, Large medical practises Forensic Departments Environment and human health Human Metab Research Universities Foodomics Food Industry

The World of standardized Metabolomics NMR (SOP and fieldstrength) for the IVDr multi-solution platform allowing worldwide interdisciplinary exchange

IVDr-Platform+Tools 4

The IVDr Platform concept

External Partner 1 Cardiovascular Diseases In progress External Partner 2 Prostate Cancer in progress External Partner 3 Obesity/Diabetes Metabolic Syndrome In progress

External developments in R&D Ecosystem

IVDr-Platform and Standardization : Allows to combine solutions, developed by Bruker BioSpin and/or external partners

• FoodScreener

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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

Data Analysis

Operation based on complete standardization guarantees unrestricted exchangeability of data worldwide

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Enabling Tools on the IVDr Platform for automatic analysis in Plasma/Serum

IVDr-Methods SOPs for plasma and serum

B.I.LISA and B.I.QUANT-PS Fast version ~8 min One 1D-experiment B.I.LISA and B.I.QUANT-PS Standard version ~ 18 min 2*1D-experiments + 2D-J-Resolved B.I.BiobankTool (QC) B.I.QUANT-PS B.I.LISA Complete Package

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

Output of B.I.QUANT-PS consists of 26 parameters listing the concentrations for Plasma/Serum in detail. Such analysis supports research and produces invaluable input in:

Epidemiology Frequent health problems like cardiovascular diseases, diabetes and cancer Ability to monitor and optimize treatment Food related changes in Plasma/Serum Composition show influence

• n health

Information about personalized profile in plasma/serum Biobanks

B.I.LISATM

Small molecule Quantification in Plasma/Serum B.I.QUANT-PS

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• 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

Plasma/Serum Quantification in detail Example Creatinine

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Actual Sample 95% range In model set Outlier in Pyruvic Acid

Metabolite recognition and quantification under full automation

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Push button automation From measurement to final report. Shown are examples for the automatic Fit

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

• f 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)

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Lipoprotein Subclass Analysis B.I.LISATM in health/disease related research

B.I.LISA supports research and produces invaluable input in:

Diabetes type 2,

• besity,

metabolic syndrome Cerebrovascular Diseases Cancer (e.g. via blood triglycerides) Inflammatory Diseases General Cardiovascular diseases ( in prevention, early detection and treatment) Alzheimer (APO-A1 binds Amyloids) Thrombosis Atherosclerosis Stroke High blood pressure Fatty Liver disease

B.I.LISATM

Food/environment and health 12

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

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Control sample

Donor had cardiovascular event 3 days after blood collection

Recognize cardiovascular risks in time to prevent incidents

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Innovation with Integrity

Longitudinal NMR Reproducibility ringtest on 11 IVDr platforms in 5

• rganizations on lipoprotein analysis

NCEP Criteria for Lipid and Lipoprotein Testing Instrument specific variance in QC samples

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Improve your value proposition: Add B.I.QUANT-URTM for every urine sample Bruker IVDr Quantification in urine. Can be combined with B.I.LISATM on the same platform

The output of B.I.QUANT- URTM consists of up to 150 parameters describing the metabolite composition in urine in detail. Such analysis supports research and produces invaluable input in:

Epidemiology Frequent health problems like in diabetes, metabolic syndrom, kidney and cancer Ability to monitor and optimize treatment Food related changes in urine metabolite Composition show influence on health Information about personalized profile in urine Biobanks

B.I.Quant-URTM

Urine Quantification B.I.QUANT-URTM

Report Excerpts

B.I.Quant-URTM

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

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Biobanks and NMR

NMR can provide added value to biobanks:

Extensive QC of Incoming samples Offer metadata Selected spectra from inventory Support Clinical trials with spectra instead

• f aliquots to

measure Build compatible spectra inventory To other biobanks ww Build compatible Spectra base with Phenome centers QC process Generates NMR Data for storage in the biobank Add Analysis Results to spectra And metadata: e.g. Urine Quant. Lipoprotein Subclass Analysis Sort out Aliquots with Low quality Support development Of new diagnostic routines

NMR for Biobanks

Gain new funding possibilities 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

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