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© 2017 Artel1
© 2013 ARTEL
Environmental Impact
on Liquid Handling
Pascal Silversmet, GSK
Katie Haith, Tecan
George Rodrigues, Artel
GSK : Who we are
Pharmaceuticals
We develop and make
medicines to treat a range of
conditions including respiratory
diseases and HIV/AIDS
Vaccines
We research and make
vaccines for children and
adults that protect against
infectious diseases
Consumer Healthcare
We make a range of consumer
healthcare products in four
categories: Wellness, Skin
health, Oral health and Nutrition
2
2bnpacks of medicines
in 2016
833mdoses of vaccines
in 2016
5bnconsumer healthcare products
in 2016
Source: GSK 2016 Annual Report
Our global presence
3
Hamilton
Saint-Amand-Les-Eaux Dresden
Moscow
Nashik
Gödollö
Ste Foy
Wavre
Rixensart
Hamilton
Marietta
Marburg
Rosia/Siena
Tian Yuan (JV)
Shanghai
Singapore
Ankleshwar
Manufacturing
Facilities
Our global presence
4
Hamilton
Saint-Amand-Les-Eaux Dresden
Moscow
Nashik
Gödollö
Ste Foy
Wavre
Hamilton
Marburg
Tian Yuan (JV)
Shanghai
Singapore
Ankleshwar
Manufacturing
Facilities
Global R&D
Centers
Rockville
Rosia/SienaMarietta
Rixensart
EasyLab Global support to R&D
Global automation park
5
USA
BRA
CHN
CAN
- 450 users
- >80 running systems
- 7 countries, accross 3 continents
Marburg
RDC BelgiumEASyLab Centre of
Excellence
RDC US
RDC Italy
EasyLab : Engineering Automated Systems for Laboratory
Mission
6
Support Global R&D in :
Integrate Automated Solutions into Lab Processes with a
end-to-end service and harmonization mindset
Design Phase
Development Validation
LCMImplementation Phase
Project
EasyLab Expertise
• Liquid Handling (topic of today)Sample preparation & Predilution, Serial Dilution, Plate Filling & Reagent dispensing,
Aliquoting, Formulation and pH measurement, …
• Image AnalysisCells based assay reader: Seroneutralisation, Titration, Elispot, SRD, Bactericide,
Hemaglutination,…(Fluorescence, multiplex,…)
• Automated Label printing & Sample Management
• Customized Robotics solution
• Innovative technologies : Artificial Intelligence, Augmented Reality …
• Computer System Validation (Up to GMP level)
Main Technological Expertise Field
7
Liquid Handling : Precision/accuracy qualification
Case study : Laval 2015 (Canada)
8
Clinical Lab equipped with 6 TECAN Liquid handling systems
Systems are working days and night to produce Clinical results
Situation
•Nobody in the Lab the weekend STOP HVAC (air conditioning) in lab WE
•Canada winter -40°C and summer +40 ° extreme different environment conditions
Ecological initiatives in
2015
to save energy
•Suddenly, Assays performed on LH systems on Monday systematically out of range
•Consequence : No more testing on Monday decrease productivity & trust in automated systems
•After investigation : Humidity/pressure/temperature required all Monday to recover. No real human sensitivity but LH systems affected.
Issue
Liquid Handling : Environmental impact
As global organization EASyLab transfer system/protocol to other GSK sites and countries
different weather conditions and to workaround we need :
– Environment Automatic Liquid Handling parameters adjustment or
– At least monitor temperature/pressure/humidity for further investigation
Partnership between ARTEL-TECAN-GSK to Modelize impact of environment on LH
based on Design of Experiment approach where :
– GSK provided statistical design
– Tecan provided equipment and liquid handling expertise
– Artel provided environmental chamber, and conducted testing and data analysis
Partnership TECAN-ARTEL-GSK
9
SOFTWARETEST MATERIALS
HARDWARE
QC Kit components
Freedom EVOware®
QC Kit Wizard
Barcode
Scanner
ShakerReaderCalibrator plate
12
QC Kit
Verification Plates
(96 well & 384 well)
QC Kit
Solutions
QC Kit Sample Solutions & Diluent
• Contain 2 dyes: Diluent and Range Solution
• Distinct absorbance maxima (520 & 730 nm)
• Different concentrations of Range (red dye)
for different volume ranges
• Diluent (blue dye) at same concentration for
all ranges
• Stable and traceable to the National Institute
of Standards and Technology, USA (NIST)
13
QC Kit Verification Plates
• Lot characterized plates
• Extensive testing of every plate lot
• Well dimensions traceable
to the National Institute of Standards
and Technology, USA (NIST)
• Bottom diameter (D) and taper angle ( )
are critical to volume calculations
• 2D barcode on plate boxes carries
necessary information about
performance, dimensions and lot
number
14
D
15
How it works - Overview of Dual-Dye Photometric
Method
• 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
• The Tecan Infinite reader measures absorbance
at 520nm and 730nm
• Based on the optical density (OD)
measurements, the absolute volume of pipetted Range
Solution is calculated
• This calculation factors in data gathered from
the Calibration and Baseline steps
Patented dual-dye Ratiometric™ technology from Artel
16
QC Kit Software for EVOware
• Fully integrated with Freedom EVOware, enabling seamless, step-by-step control of the
entire workflow.
• A wizard controls pipetting, shaking, reading, data analysis and reporting, providing a
straightforward pass/fail result.
17
QC Kit Reporting
• Is designed to meet quality and regulatory needs with the following reporting
options:
• QC Kit report –one page summary of the verification test results and a
pass/fail analysis
• QC Kit extended data report – for more detailed, systematic analysis of
liquid handling verification results, to be used for troubleshooting and liquid
handling optimization
18
QC Kit Report
19
OVERALL QC REPORT TO SATISFY
QUALITY AND REGULATORY
NEEDS
• Consists of:
• User Information
• Instrument information
• Software version information
• Pass/Fail requirements
• Average test results for all
channels
The reports can be printed or exported
to the PDF file format.
The data can also be exported as CSVs
for further analysis, such as trending
or data driven troubleshooting.
QC Kit Extended Data Report
20
THE AUTOMATICALLY GENERATED PRINTOUTS LISTS THE OVERALL ACCURACY AND
PRECISION (CV) AND GIVES VOLUME INFORMATION PER TIP
• Report shows the overall outcome (pass or fail)
• Color coding shows results for each individual well at a glance
• Easy to identify if a tip deviates from the expected volume
Reliable Quality Control
QUALITY CONTROL ENSURES THAT YOUR INSTRUMENTATION’S PIPETTING RESULTS
ARE CONSISTENT AND COMPARABLE
• Consistent – Proves that your instrument is performing well over time,
whether that is weekly, monthly or annually
• Comparable – Shows that pipetting performance is similar to other
pipetting devices
• Demonstrates that your Freedom EVO® is performing as intended
22
© 2017 Artel25
© 2013 ARTEL
Two Quantitative Responses
• Precision (percent CV)
• Trueness (percent systematic error)
© 2017 Artel27
© 2013 ARTEL
Some Constant Inputs
• One liquid handling system
• One liquid type (aqueous)
• One syringe size
• One dispense method
• One elevation (barometric pressure)
© 2017 Artel28
© 2013 ARTEL
Three Controlled Input Variables
• Temperature – quantitative
• Relative Humidity - quantitative
• Volume Arrangements - categorical
© 2017 Artel29
© 2013 ARTEL
Three Tip Sizes
Code Tip Size Volume
V1 1000 200
V2 200 100
V3 200 25
V4 200 10
V5 50 25
V6 50 10
Configuration
© 2017 Artel30
© 2013 ARTEL
Four Test Volumes
Code Tip Size Volume
V1 1000 200
V2 200 100
V3 200 25
V4 200 10
V5 50 25
V6 50 10
Configuration
© 2017 Artel31
© 2013 ARTEL
Nine Environments
• Temperature Three Levels
• 15, 22.5, 30 °C
• Relative Humidity Three Levels
• 30, 55, 80 %RH
© 2017 Artel33
© 2013 ARTEL
Six Volumes at Each Environment
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
© 2017 Artel34
© 2013 ARTEL
Plus Replicates
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
V1V2V3V4V5V6
© 2017 Artel37
© 2013 ARTEL
Example of one QC Kit test result
199 1 2 3 4 5 6 7 8 9 10 11 12
A 202.3 202.1 202.2 202.6 202.5 202.3 202.7 202.4 201.9 201.9 201.7 199.9
B 203 203.1 202.7 202.5 202.6 202.8 202.4 202.8 202.3 202.5 202.1 202
C 202.2 202.2 202.2 202.4 202.3 202.6 202.4 202.6 202.1 202.4 201.7 202.3
D 201.1 200.6 200.5 200.8 201 200.9 201.3 201.3 201.1 200.7 200.5 200.8
E 201.6 201.5 201.5 201.7 201.9 202.5 202 202 202.1 202.1 201.3 202.5
F 201.6 201.3 201.5 201.7 202.1 202.1 202.6 201.8 201.8 201.6 201.5 202.2
G 202.6 202 201.9 202.8 203.1 202.8 203.1 203.4 202.7 202.9 201.8 203.3
H 201.3 200.9 200.7 201.3 201.2 201.9 201.5 200.9 201.1 201.7 201.3 201.7
PrecisionStd Dev = 0.71 µL
CV = 0.35%
TruenessMean Volume = 201.93 µL
Systematic Error = + 0.97%
© 2017 Artel56
© 2013 ARTEL
Calculate Evaporation Potential
Temp P sat RH P vap P evap
C kPa % kPa kPa
30 0.51 1.20
55 0.94 0.77
80 1.37 0.34
30 0.82 1.92
55 1.50 1.23
80 2.19 0.55
30 1.28 2.98
55 2.34 1.92
80 3.41 0.85
1.71
2.74
4.26
15
22.5
30
© 2017 Artel61
© 2013 ARTEL
200 µL Tip at 100, 25 and 10 µL
100 µL Delivery
25 µL Delivery
10 µL Delivery
© 2017 Artel68
© 2013 ARTEL
Sensitivities in order
Code Tip Size Volume
V2 200 100 -1.0%
V5 50 25 -1.6%
V1 1000 200 -1.7%
V6 50 10 -2.6%
V3 200 25 -2.8%
V4 200 10 -3.7%
Configuration Sensitivity
per kPa
© 2017 Artel69
© 2013 ARTEL
Conclusions1) Environmental conditions impact any pipetting that incorporates air.
2) Precision was found to be insensitive to temperature and humidity over the
testing range.
3) Trueness was found to depend on the environmental conditions
a. Trueness should be optimization under the local environmental conditions
b. A linear correlation was found between the trueness and the evaporation
potential
c. Fuller tips are less sensitive
c. A stable environment will minimize impact on the business process
4) The QC Kit is unaffected by the environmental conditions.
© 2017 Artel70
© 2013 ARTEL
Final NoteThe precision of the Tecan Freedom EVO ® was found to be
insensitive to environmental conditions and performed within
manufacturer’s limits over the entire range tested in this
study (15 °C to 30 °C and 30% to 80% relative humidity).
Note: Tecan specifies the pipetting behavior of the Freedom
EVO ® under controlled environment 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.