2DS01
Statistics 2 for Chemical
Engineering
Contents
• high-throughput screening • combinatorial chemistry
Breakthrough in experimentation
• robotic sample preparation • miniaturization of reactors
• high-level automatization of sensors • pharmaceutical industry:
– routine creation and testing of 1000 to 1000000 distinct compounds (libraries)
• techniques are now also being applied in material development
• new companies:
– Symyx (www.symyx.com)
High-throughput screening
• typical cycle of experimentation:– thousands of reactions in few hours – few hours of statistical analyses
– thousands of reactions in few hours – few hours of statistical analyses
–
---• new chemical may be developed in 3 weeks rather than 3 years
• Which statistical techniques are important?
• How do the classical techniques of the previous lectures fit in?
Overview of experimental strategies
designs for non-linear models
project
• 4 different catalysts, 10 continuous change equivalence: 0.01-0.10, with mixtures:
• 4 different bases, 10 continuous change equivalence: 0.01-0.10, with mixtures
• 3 solvents
• temperature: 50C-120 C, steps of 10 C
• 3 choices for both X and R1
• 6 choices for R2
synthesis
• structural descriptors are calculated for each compound
• similarity coefficients are calculated between compound pairs
• compounds are selected using multivariate methods (based on clustering, dissimilarities, etc.)
development
• currently descriptors less well developed (complex interactions / processing)
• need for other strategies
Common approaches:
1. High-speed array strategies
High-speed array strategies
1. gradient arrays
2. quaternary mask arrays
Gradient arrays
100% B
100% A
100% C
• continuous spread
Quaternary mask arrays
designs
• cost of experimentation is low
• high resolution designs are possible
– full factorials
– central composite designs
– special cubic mixture designs
• 3rd and higher order interactions are
important !
• use in second stage of screening (after “hit” has been found)
True combinatorial design strategies
• split-and-pool / split-and-combine • representational strategy
• index library strategy
Representational strategy
• similar to
one-factor-at-a-time strategy
Index library strategy
All 2-way combinations strategy
• 19*18/2 = 171
N-way combinations
• gain possible by noting that 1 2 3 4 5 contains
– 10 2-way combinations – 10 3-way combinations – 5 4-way combinations
chemistry
• http://www.combichem.net/ • Homepage of Furka:
http://szerves.chem.elte.hu/Furka/ •
http://www.aae.enscm.fr/anciens/94-mc/combchem.htm
• http://www.combinatorial.com/ • Molecular diversity page:
http://www.5z.com/divinfo/ • Links to several papers:
Literature
• J.N. Cawse, Experimental Strategies for Combinatorial and High-Throughput Materials Development, Acc.
Chem. Res. 34 (2001), 213-221
• R. Hoogenboom et al., Combinatorial Methods,
Automated Synthesis and High-Throughput Screening in Polymer Research: Past and Present, Macromol.
Rapid Commun. 24 (2003), 15-32
• G-J.M. Gruter et al., R&D Intensification in Polymer Catalyst and Product Development by Using High-Throughput Experimentation and Simulation,
Macromol. Rapid Commun. 24 (2003), 73-80.
• W.A. Warr, Combinatorial Chemistry and Molecular
