© 2016 Artel 1

Impact of Standardizing on Traceable QC

for Volume Transfers

© 2016 Artel 2

How is liquid handler performance evaluated in your lab?

What information do you obtain (accuracy and/or precision)?

How long does it take?

How much does it cost?

Who takes ownership?

Are you confident that every liquid handler within your organization

dispenses equal volumes?

Are you confident that your liquid handler QC method is performed

reproducibly across your organization?

The challenges

© 2016 Artel 3

“In the modern drug discovery, clinical, and forensic laboratories there

is an ever-increasing requirement for validation of every aspect of

laboratory operations …

A single error in a liquid transfer step can destroy a complete

assay, and in most cases, this error is not caught until the assay is

completed resulting in a loss of time and resources ....”

G.J. Wendel, J. Assoc. Lab. Autom., 2006, 11, 88-91

Liquid Handling Validation

© 2016 Artel 4

Goal:

Reproducibly deliver target volume

with accuracy & precision

Solution:

Rapidly verify transferred target

volumes with a standardized,

traceable platform technology

Tecan QC Kit

Artel MVS

© 2016 Artel 5

Automation-ready MVS

A Standardized QC Platform:

Traceable

Fast & Easy

Accurate

Precise

Known Performance

Data Integrity

© 2016 Artel 6

Process Work Flow:

Checking Volume Transfer Performance

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Increase Liquid Handling Quality – Simply By

Knowing Performance

Dispense Dye

Solutions and

Mix.

Read Plate. Know

Performance.

© 2016 Artel 8

Dual-Dye Photometric Method: Dispensing and

Reading

• Photometric measurement of liquid volume

• Two dyes measured at two wavelengths

• Ratiometric calculation of results per well

• Simultaneous measurement of accuracy & precision per tip

• Artel’s patented dual-dye ratiometric photometry is included in ISO 8655:

Part 7 and the measurement results are NIST-traceable

Mix

Photometric Measurements

Dispense Sample (quantitative)

Dispense Diluent (non-quantitative)

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Liquid handler

Reagents

Tips

Environment

Operator

contribute directly to the liquid

dispensing variability

affect the

measurement process

Mixing

Detector

Plate Type

Sources of Variability for Liquid Handler

Calibration Measurements (1 of 2)

© 2016 Artel 10

Sources of Variability for Liquid Handler

Calibration Measurements (2 of 2) A Standardized QC Method Removes Many Variables

Liquid handler

Reagents

Tips

Environment

Operator

contribute directly to the liquid

dispensing variability affect the

measurement process

Mixing

Detector

Plate Type

© 2016 Artel 11

Standardization Allows for Accuracy Comparisons:

Accuracy Matters

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Defining Accuracy & Precision: There is a Difference

5 µL target

volume; 8 µL

dispensed with

repeatability

5 µL target

volume; 5 µL

dispensed with

repeatability

5 µL target

volume; 5 µL

averaged

dispense without

repeatability

5 µL target

volume; 8 µL

dispensed

without

repeatability

precise,

not accurate

precise

& accurate

accurate,

not precise

not precise,

not accurate

© 2016 Artel 13

Example:

Liquid Handler* QC Volume Information

Albert & Bradshaw, J. Assoc. Lab. Autom., 2007, 12, 172 – 180.

All tests have similar precision, but varying accuracy

6.80 mL

9.97 mL

* not a Tecan instrument

© 2016 Artel 14

40 mL total working volume

% difference in compound concentration = 37.9%

(6.80 mL)(2 mM)/(40 mL) = 0.34 mM vs. (9.97 mL)(2 mM)/(40 mL) = 0.499 mM

Knowing Accuracy, and Therefore, Concentration

6.80 mL of a 2 mM

compound

9.97 mL of a 2 mM

compound

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40 mL total working volume (± 4 mL)

% difference in compound concentration = 56.8%

(6.80 mL)(2 mM)/(44 mL) = 0.309 mM vs. (9.97 mL)(2 mM)/(36 mL) = 0.554 mM

6.80 mL of a 2 mM

compound

9.97 mL of a 2 mM

compound

+ 4 mL - 4 mL

Knowing Accuracy, and Therefore, Concentration

© 2016 Artel 16

Standardizing on a QC Platform Allows for

Direct Comparisons….

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Standardization: Multiple User Types

Research and development

High throughput screening & compound management

Food & agriculture

Automated liquid handler manufacturers

Automation engineers

Service, production support, manufacturing

Clinical

Forensics

Government

Other

© 2016 Artel 18

A (Global) Standard Measurement Platform

5 mL, 8-tip LiHa 5 mL, 96-tip MCA

Images from: www.tecan.com

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CAMBRIDGE, UK SAN DIEGO, CA

=

Compare performance regardless of user, model, date or

location…remove robot-to-robot differences

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Corrective actions are easier to implement

Comparability (local, off-site, global)

SAT, FAT, Process control

Transferability between methods, devices, assays, groups

Reduction in errors, re-work

Monitoring accuracy and precision with ability for trending analysis

Ability to pick the best device for the task

Confidence, take the guess-work out of liquid handling QC

Removing ‘blame game’ – improves communication(s)

Known uncertainties, shelf-life, etc. with measurement tool(s)

Impact of Standardizing on Traceable QC

for Volume Transfers

Tecan QC Kit

OVERVIEW AND OPERATION

Automated Quality Control with QC Kit

• Easy to use

• Fast

• Comprehensive data

• Traceable

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Consumables

QC VERIFICATION PLATES

• Two Formats: 96-well and 384-well

• Lot characterized plates

• Extensive testing of every plate lot

• Well dimensions are characterized through certified

reference materials maintained by NIST; this ensures

traceability to SI

• 2D barcode on plate boxes carries necessary

information about performance, dimension, and lot

number

QC RANGE SOLUTIONS

• Kit contains two Dyes: red and blue

• Distinct absorbance maxima: 520 & 730 nm

• Different concentrations of red dye for

different volume ranges

• Stable and traceable to international standards

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Calibrator Plate and Reader

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• Sealed precision cuvettes filled with same dyes as sample solutions and diluent

• Barcoded absorbance traceable to international standards

• Calibration of reader ensures consistency before runtime

• Tecan Infinite reader:

• Infinite F50 for 96 well plates

• Infinite 200 PRO for 96 & 384 well plates

• Narrow bandwidth filters

Easy to Use

CONVENIENT AND SECURE

• Step by step software guidance with clear

instructions eliminates mistakes and reduces

training time to a minimum

• Pre-mixed solutions; open and use

• Verified hardware selected specifically for QC

• Built in reporting module generates automatic

reports

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Fast

START, MEASURE, REPORT

• No need for sample preparation, standard curve

generation, and post-measurement calculation

• Testing of one volume takes:

• <15 min for standard liquid handling arm (1 plate)

• <15 min for MultiChannel Arm™ 96 (3 plates)

• <15 min for MultiChannel Arm™ 384 (3 plates)

• Frequency

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Comprehensive Data

LIQUID HANDLING AND

PERFORMANCE DATA

• The automatically generated

printout lists overall accuracy

and precision (CV) and gives

volume information per tip

• Report shows the overall

outcome (Pass or fail)

• Color coded “heat map”

• Easy to identify if a tip

deviates from the expected

volume

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Traceable

TRACEABLE RESULTS FOR REGULATORY

COMPLIANCE

• Consumables

• QC Kit test results are traceable to

international standards and can be compared to

the manufacturer's specification used for IQ/OQ

• Benefits include

• Traceability enables compliance with regulatory

standards for peace of mind for upcoming audits

• Comparison of liquid handling data between different

sites

• Compare instruments within the company;

mandatory for protocol transfer from R&D to quality

control and production

• QC Kit tests before running important assays will

remove any question of pipetting robot in case of

surprising results

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Software

THE QC KIT SOFTWARE IS AN EVOWARE

ADD-ON

• EvoWare

• Automated with Freedom EVO liquid handler

• It functions as a wizard to help the user at run-

time

• Value

• Security and Convenience

• Time Savings

• Comprehensive Results

• Consistent

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Automated workflow

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Calibrator, Baseline, QC Plate

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Pipetting & Volume Verification Success

Failure

TROUBLESHOOTING LIQUID HANDLER

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Results

Advantages

• Fast, Easy, comprehensive

• QC Kit is integrated with

EVOware and supported by

Tecan

• The software includes verified

pipetting templates for common

configurations

• The QC Wizard will automatically

execute the pipetting, shaking,

measuring, reporting

• Traceable components

• Traceable results

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Environmental Testing of Tecan EVO using the QC Kit

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Experiment - Environmental Conditions Tested

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Experiment - Volumes Tested

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Measured Volumetric Performance

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Trueness

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Conclusions Precision of the Tecan Freedom EVO was found to be insensitive to environmental conditions Trueness does depend on environmental conditions. Trueness exhibited a linear correlation with the “evaporation potential” Although the Tecan QC Kit is intended to be used for checks such as IQ/OQ, this study shows that the Tecan QC Kit can also be used for performance checks under environmental conditions that deviate from the manufacturer’s specified operating conditions. note 1: Tecan specifies the pipetting behavior of the Tecan Freedom EVO under controlled environmental conditions (T = 20 °C to 27 °C; relative humidity at 25 °C between 30% and 60%). Volumetric performance specifications apply to this controlled limit. For operation outside these limits, meeting the manufacturer’s specifications for volumetric performance is not guaranteed.