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11 © 2009 PerkinElmer© 2009 PerkinElmer© 2009 PerkinElmer© 2009 PerkinElmer
Ronald Edler, Jan ter Wiel
May 2009
Quality Control in LSCApplications in cocktail production
22
PerkinElmer Groningen, NetherlandsPerkinElmer Groningen, Netherlands
42 people
Production of 3 product groups
6 scientists for production support and development (chemistry / biology)
Global distribution
PerkinElmer Groningen… 3 product groupsPerkinElmer Groningen… 3 product groups
33
1. Microplates
� Complete range of standard
microplates
� Clean room processing in
Groningen (FlashPlates,
LumaPlates, barcoding,
custom plate coating)
PerkinElmer Groningen… 3 product groupsPerkinElmer Groningen… 3 product groups
44
2. Luminescence Reagents
� LITES reagents based on
luciferase reaction
� For reporter gene assays,
cell proliferation, kinase
assays
PerkinElmer Groningen… 3 product groupsPerkinElmer Groningen… 3 product groups
55
3. LSC Cocktails and Supplies
� Widest range of LSC cocktails with
over 35 years of history:
� Complete range of glass and
plastic vials for counting
� Developed, produced and
supported from Groningen!
Packard BioScience e.g. Ultima Gold range, PicoFluor range
WALLAC e.g. HiSafe range
NEN e.g. Atomlight
PerkinElmer Groningen… 3 product groupsPerkinElmer Groningen… 3 product groups
66
PerkinElmer Groningen… leader in LSCPerkinElmer Groningen… leader in LSC
Product groups:Product groups:
LSC Cocktails and Supplies
Widest range of LSC cocktails with over 35 years of history:
Packard BioScience e.g. Ultima Gold range
WALLAC e.g. HiSafe range
NEN e.g. Atomlight
LUMAC e.g. RiaLuma, AquaLuma
Complete range of glass and plastic vials for counting
Developed, produced and supported from Groningen
77
Production of LSC Cocktails
� Cocktail raw materials:
� Incoming QC inspection using for
instance FTIR Spectrum 100
� Testing on colour, LSC
background, efficiency, etc.
Solvents ‘safe’ / ‘classical’ energy transfer
Surfactants many different types sample uptake
Scintillators primary / secondary wavelength shift
PerkinElmer Groningen… leader in LSCPerkinElmer Groningen… leader in LSC
88
Production of LSC Cocktails� Dedicated vessels for cocktail preparation
• 400 to 5000 L vessels
• Explosion-safe equipment
• Chemical treatments to improve performance by removing colour, reducing
luminescence, reducing quench
PerkinElmer Groningen… leader in LSCPerkinElmer Groningen… leader in LSC
999
LSC Cocktail production/quality
� Final QC inspection – performance (eff., bkgd, sample uptake)
� Retention samples
� Dispensing in 5L cans, bottling in glass
� Storage and worldwide distribution (TNT + Fedex)
PerkinElmer Groningen… leader in LSCPerkinElmer Groningen… leader in LSC
1010
A. 40K-contamination of nonylphenolethoxylates (NPE):
• NPE’s are bulk chemicals used for laundry detergents and cleaners
• Low-cost production in a competitive market is required
• As a result, low-cost potassium catalysts are nowadays used in the production of NPE’s
• NPE’s are important components of most LSC cocktails
Ongoing LSC Quality IssuesOngoing LSC Quality Issues
1111
A. 40K-contamination of nonylphenolethoxylates (NPE):
• Quantulus detects these contaminants in Low Level mode (Turku results)
• Ch. 5 – 200 = 3H (+ luminescence) / Ch. 200 – 1024 = 40K
• Careful selection or dedicated production of NPE’s is required
...uantulus\IGLACT1\S
...uantulus\IGLACT1\S
...uantulus\IGLACT1\S
...uantulus\IGLACT1\S
...uantulus\IGLACT1\S
...uantulus\IGLACT1\S
Sample Spectrum
1,000900800700600500400300200100
0.022
0.02
0.019
0.018
0.017
0.015
0.014
0.013
0.012
0.01
0.009
0.008
0.006
0.005
0.004
0.003
0.001
0
-0.001
-0.003
-0.004
Ongoing LSC Quality IssuesOngoing LSC Quality Issues
1212
B. Environmental ban on the use of nonylphenolethoxylates (NPE):
Endocrine disruptions in Aquatic Environment
� EEC regulations Nonylphenol Ethoxylates (1992)
� European directive 2003/53/EC : level < 0.1 %
USA
� C&EN june 2006, discussion on ban in the US
Environmental Issues of SurfactantsEnvironmental Issues of Surfactants
1313
B. Environmental ban on the use of nonylphenolethoxylates (NPE):
� Reformulation of LSC cocktails to avoid NPE’s is required
� Alcohol ethoxylates are considered as alternative surfactants
� Reformulations ongoing,
� PicoFluor-15
� Focus on efficiency
� background
� Sample load capacity 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0
Serum
0.1 M Imidazole (pH=7.4)
0.1 M HCl
10 % TCA
0.25 M Amm. Acetate
0.1 M Sodium Sulphate
0.04 M Sodium Phosphate
0.1 M PBS
0.5 M NaOH
0.1 M NaOH
Digoxin
0.05 M Tris/HCl
0.01 M PBS
0.15 M NaCl
water
Pico Fluor 15 Pico Fluor 15 New
Ongoing LSC Quality IssuesOngoing LSC Quality Issues
1414
C. 14C contamination by chemical components from bio-origin:� Alcohol ethoxylates and other chemicals can be manufactured using fatty
alkohols of natural origin� Availability of bio-chemicals is increasing - cost is reducing� Bio-chemicals contain 14C in contradiction to chemicals from fossil oil
chemical origin
0
5
10
15
20
Nonylphenol
ethoxylate
Fatty alkohol
ethoxylate
Alkohol
ethoxylate
Alkohol
ethoxylate
Synthetic alcohol
ethoxylate
Fatty alkohol
ethoxylate
cp
m
counts in C 14 region
LSC Issues: Renewable Chemical SourcesLSC Issues: Renewable Chemical Sources
1515
LSC : surfactants quality controlLSC : surfactants quality control
QC methodologies / requirements for Nonylphenol Ethoxylates ( NPE’s)
•Color in product
•Counting characteristics in LSC
•Background development with sample
•Salt content in the surfactants
Test Methodology
•20 gram Sample•30 gram Standard Pseudocumene (Pseudocumene, PPO, Bis-MSB)
•Measure in Low level ( TriCarb)
1616
LSC : surfactants quality controlLSC : surfactants quality control
Background in low level counting mode
Heating Sample 0 - 18.6 0.5 - 5 0 - 156 %Lum
none Cycle 1 4,35 2,53 5,85 20
Cycle 2 4,47 2,63 5,9 15
Cycle 3 4,32 2,32 5,78 16
100 °C Cycle 1 3,87 2,20 5,18 18
Cycle 2 3,92 2,25 5,48 17
Cycle 3 4,00 2,03 5,47 17
150 °C Cycle 1 179,00 173,00 180,00 100
Cycle 2 101,00 99,00 103,00 100
Cycle 3 71,00 69,00 72,00 98
• Heat treatment of Surfactants
• Surfactant low level background after heating at 100 and 150 °C
1717
LSC : surfactants quality controlLSC : surfactants quality control
Quantulus : Graph of counts observed of different surfactants� Full spectrum
1818
LSC : surfactants quality controlLSC : surfactants quality control
Quantulus : Graph of counts observed of different surfactants� Random signals
1919
C. Renewable source ethanol� Renewable sources of chemicals available� Main emphasis on ethanol� Ethanol applied in production of chemicals
0
5
10
15
20
25
30
Blank cocktail Ethanol 96 % TEP lot 1000 TEP lot 087 TEP lot 1008 Jenever
counts in C 14 region
cp
m 0
-15
6(L
L)
LSC Issues: Renewable Chemical SourcesLSC Issues: Renewable Chemical Sources
2020
D. 14C presence in chemical components from bio-origin:� Example of 14C presence in Triethyl phosphate made with bio-ethanol
0
5
10
15
20
nd 1/08114 CHI/29075 CHI/12095 CHI/08066 CHI/08017 CHI/30035 cocktail
cpm samples raw material
cp
m
lot numbers0 – 18.60 – 156
LSC Issues: Renewable Chemical SourcesLSC Issues: Renewable Chemical Sources
2121
D. 14C presence in chemical components from bio-origin:� Example of 14C presence in Chemicals from bio origin
LSC Issues: Renewable Chemical SourcesLSC Issues: Renewable Chemical Sources
2222
PerkinElmer Groningen
...continued support and commitment...continued support and commitment
SUMMARY:SUMMARY:
�� Changes in legislation and the world chemical market requires cChanges in legislation and the world chemical market requires continueing support and efforts in ontinueing support and efforts in
LSC countingLSC counting
�� PerkinElmer continues its focus on LSC Quality PerkinElmer continues its focus on LSC Quality
�� This can only be achieved by continuously monitoring the qualityThis can only be achieved by continuously monitoring the quality and applications of its products and applications of its products
and a proactive approach and a proactive approach
2323
RRD Specialists
Associate Product Leader Associate Product Leader ––
Chuck Passo, Downers GroveChuck Passo, Downers Grove
Tel.: +1Tel.: +1--630630--322322--54005400
Mobile: +1Mobile: +1--815815--483483--18261826
[email protected]@perkinelmer.com
Chuck in the box
Ronald EdlerRonald Edler
European Line Leader Radiometric DetectionEuropean Line Leader Radiometric Detection
Mobil: +49(0)172Mobil: +49(0)172--63859096385909
Email: Email: [email protected]@perkinelmer.com