Waters’ clinical solutions

1 2015 Waters Corporation 1 Waters clinical solutions Automating and Integrating Sample Preparation with LC/MS and Software connection to the LIMS Dr. Simone Donzelli Health Sciences Business Development Manager Southern Europe 2015 Waters Corporation 2 Outline Sample Preparation Needs and Strategies Product Portfolio for Integration of Sample Prep and LC/MS Offline Sample Preparation oOffline Automated Sample Preparation System (OASPS) Product Features Applications Example of the Effects of Automated Sample Preparation 2015 Waters Corporation 3 Sample Preparation for LC/MS Prevailing attitude in many laboratories is to do as little sample prep as possible because sample prep is seen as: Costly, labor intensive and inefficient Delivering inconsistent results Requires slow and difficult method development Uses expensive sample prep consumables If sample prep is needed many labs deploy good enough techniques Dilute and Shoot LLE/ILE Protein Crash and Shoot Try to solve assay issues with LC/MS and avoid sample prep Increased instrument downtime and service requirements Increased column consumption Solvent exposure and disposal Compromised assay results 2015 Waters Corporation 4 Many LC/MS assays require or can greatly benefit from sample prep Low level analytes Poorly ionizing analytes Complex matrices (Blood, Plasma, Saliva, Urine, Hair)

2 When using LC/MS, most laboratories inevitably reach a sample prep bottleneck More efficient sample prep processes needed for assays More throughput needed Better cost/test needed Better integration between sample prep and LC/MS Fewer errors in sample processing requiring retests To resolve their sample prep issues, labs turn to automation Sample Preparation for LC/MS 2015 Waters Corporation 5 Offline Automated Sample Preparation System (OASPS) Semi-Automated SPE Offline sample preparation Automation of many SPE steps Interface to LC/MS Moving Seamlessly from Sample to Answer: Automated Sample Preparation Products Lab Productivity Cost Benefit Method Development Lab productivity: Sample prep completely automated Creation of Worklist via barcode Cost benefit: Reasonable price/test Diagnostic kits CE_IVD at same price of the manual ones Method development Extraction s Methods created and validated from Waters 2015 Waters Corporation 6 Offline Automated Sample Preparation System (OASPS)

3 Automation of the sample prep Collaboration with Tecan and Hamilton Collaboration with Siemens and Abbott 2015 Waters Corporation 7 Freedom EVO100 Robotic Workstation Offline Automated Sample Prep System ACQUITY UPLC with TQD or XEVO Series of Mass Specs Dedicated System for SPE Sample Preparation and LC/MS Analysis 2015 Waters Corporation 8 Offline Automated Sample Preparation Automation System Features 4-Tip independent liquid handling arm equipped with liquid level detection Robotic gripper arm for Oasis Elution SPE plates Two position vacuum manifold Single position plate shaker Barcode scanner for tubes Reagent trays for solvents and wash solutions _____ Pre-loaded SPE pipetting script(s) File Converter to automatically generate sample list for LC/MS 2015 Waters Corporation 9 Uncapped Tubes are Loaded onto Freedom EVO100 Deck Tube Barcodes Read Automatically Samples aliquoted into Plates for Protein Precipitation Organic Solvent Added and Plates Shaken Operator transfers Plate to Centrifuge to Pellet Proteins Operator Puts Plate back on Freedom EVO100 Deck SPE Plates Conditioned Samples loaded onto SPE Plates SPE Plates Washed as Needed Samples eluted from SPE Plates into Collection Plate Collection plate transferred by operator to ACQUITY Sample Manager Sample list generated by Freedom EVO for import to MassLynx Samples analyzed by ACQUITY System Operating Script available for Oasis 96 Elution SPE Plates Automation offline Tecan 2015 Waters Corporation 10 Benefits of Offline Automated Sample Preparation System Automation of liquid handling and plate

4 Manipulation Minimized manual intervention Flexibility to prepare multiple types of analytes easily Can perform protein precipitation, SPE, derivatisation Convenient interface with LC/MS Small footprint Robust and easy to use System 2015 Waters Corporation 11 Comparison of Automated vs. Manual SPE Methods Manual SPE Method Automated Sample Preparation Processing Time 2-4+ Hours/96 Samples <2 hrs/96 Samples Analyst Intervention Requirement 100% Involvement 10% Involvement Reported Assay Precision Typically 2-5% Typically < Exposure to Biological and Chemical Hazards Repeated and Constant Minimized with Automation Opportunity for Sample Processing Errors Multiple Points of Potential Error Minimal 2015 Waters Corporation 12 Application Examples 2015 Waters Corporation 13 Application Examples Vitamin D and Metabolites Biogenic Amines Metanephrines Drugs of Abuse Opiates Benzodiazopenes Canabinoids oMetabolites oSynthetic For research use only.

5 Not intended for use in clinical diagnostics. 2015 Waters Corporation 14 The MassLynx clinical LIMS Interface Data receiving from LIS Bi-directional interface with the most common LIS thanks to our HL-7 SW Results exported to LIS Bi-directional interface with the most common LIS thanks to our HL-7 SW 2015 Waters Corporation 15 LIMS Interfacing: What was previously possible ? .xls,.doc, .txt,.xml Import sample information in txt or Excel file Export results in txt file or XML file Procedure not allowed! 2015 Waters Corporation 16 What is the clinical LIMS Interface ? Software that allows the automated exchange of information between MassLynx and a hospital LIMS Removes the need for manual transcription of clinical information between MassLynx and a third party LIMS Conforms to Health Level 7 protocol (HL7) Version of the clinical LIMS interface was released in 2013 MassLynxLIMS Interface`LIMS`MassLynx 2015 Waters Corporation 17 The Health of your patients cannot accept errors right rignt rrgnt rront rrong wrong right right right right right right 2015 Waters Corporation 18 What is the clinical LIMS Interface ?

6 The clinical LIMS Interface allows MassLynx to be connected to a 3rd party LIMS system The LIMS Interface is a TargetLynx option that is sold and installed separately to MassLynx The option appears as a shortcut within TargetLynx menu 2015 Waters Corporation 19 3rd Party Vendors The clinical LIMS Interface has been integrated with a wide range of 3rd party drivers: Roche Diagnostics Technidata Abbott Siemens Modulab / Telepath Sunquest Inpeco Medasys Orchard Soft Computing 2015 Waters Corporation 20 What information can be exchanged? It is extremely important that Waters, the hospital and the LIMs provider all engage together to make it work Everything that could be exported in the XML file, except formulas In practice, usually only a limited range of fields are sent for example MassLynx ID HL7 Code Test ID (Job) Name of configuration OBR 4-2 Subject Text MRN PID 2 Sample Text Patient last name PID 5 Sample id Container id (barcode) OBR-2 Compound Name Compound OBR 4-4 Concentration Result OBR 20 Instrument Name Model and serial no.

7 OBR 21 2015 Waters Corporation 21 Hammersmith Hospital- Leslie Brent Lab TQD x2 and Quattro micro clinical research and TDM Connected to Sunquest LIS PC, unidirectional Installed and configured remotely Tested by the user Four drugs assays: Tacrolimus, Cyclosporine, Sirolimus, MPA Transferring the following: Test ID (Job) Name of configuration OBR 4-2 Sample id Container id (barcode) OBR-2 Compound Name Compound OBR 4-4 Concentration Result OBR 20 Instrument Name Model and serial no. OBR 21 2015 Waters Corporation 22 University of California, San Diego Xevo TQ-S x2 Standalone processing PC with LIMS Interface Connected to Soft LIS PC, unidirectional Vitamin D, Benzodiazepines, Amphetamines Currently uploading the following to Soft: Order number Patient lastname Instrument Name No Solution Flag RT Tolerance Flag Target Ratio Flag Conc Deviation Flag Compound Name Conc 2015 Waters Corporation 23 Laboratory Order Workflow: Bi-Directional Connectivity ANALYSIS REQUEST LIS/LIMS EMR 2 clinic EMR clinic 3 4 5 Waters TargetLynx (implied in Steps 3 & 4) clinical LIMS (Steps 2 and 5) Import Sample List (MassLynx) Complete Sample List Run Sample List Generate Test Results 1/6 Data Processing TargetLynx Data Analysis analyst Accept and Review Data 2015 Waters Corporation 24 Laboratory Order Workflow.

8 Tecan Tecan Printed Worklist Request 1 LIS/LIMS 2 Data Analysis analyst Data Processing TargetLynx 4 5 6 Accept and Review Data Tecan worklist to Waters MassLynx (Step 3) Waters TargetLynx (implied in Steps 4 & 5) clinical LIMS (Step 6) Generate Sample List (MassLynx) Run Sample List Generate Test Results 3 Tecan File Converter 2015 Waters Corporation 25 Workflow Software Demo 2015 Waters Corporation 29 Key Points Saves time and eliminates transcription errors entering information into LIMS Flow of information Uni-directional: send results from TargetLynx to LIMS only Bi-directional: LIMS generated worklist imported into MassLynx then send results from TargetLynx to LIMS Information is customisable Tecan Interface with clinical LIMS provides most complete sample tracking capabilities 2015 Waters Corporation 30 Questions