©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

o Offline 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)

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)

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 ® µElution 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

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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 µElution SPE Plates

Automation offline Tecan

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Benefits of Offline Automated Sample Preparation System

Automation of liquid handling and plate 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 <1.5%

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

o Metabolites

o Synthetic

For research use only. 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 2.0 of the Clinical LIMS interface was released in 2013

MassLynx

LIMS Interface`

LIMS

`

MassLynx

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The Health of your patients cannot accept errors

right rignt rrgnt rront rrong wrong

right right right right right right

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What is the Clinical LIMS Interface ?

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

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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. 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

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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

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Laboratory Order Workflow: 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

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Workflow Software Demo

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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

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Questions