Combinatorial and High-Throughput Screening of Materials ...

ACS Combinatorial Science
REVIEW
Figure 2. Examples of diversity of materials compositions, process factors, and operation conditions applicable for combinatorial screening.
(A) Dependence of the number of possible systems on the number of components. Red: systems investigated up to now. 38 (B) Factors and their
levels for one-step synthesis of diphenylcarbonate. 39 (C) Hyperspace of features of materials and measurements in chemical sensors. 40
the starting reaction components evolving into the reaction and
the dynamics of progress of multiple reactions at once at each
reaction phase. Monitoring of reaction components can provide
valuable feedback information to control and rapidly optimize
reaction parameters. Overall, in situ monitoring of combinatorial
reactions includes all of the attractive features of in-line detection
methods, such as automation, no sample removal or preparation
steps and, thus, reduced number of contamination sources. It has
been statistically demonstrated that in situ measurement systems,
in principle, are capable of making quality determinations
to a substantially higher order of precision than the traditional
54 56
off-line laboratory systems.
Optical, chromatographic, electrochemical, and mass-spectrometric
techniques are evolving as the most widely used analytical
methodologies for direct in situ monitoring and optimization of
combinatorial reactions. 57 61 A representative list of applications
of analytical techniques recently reported for the in situ monitoring
of combinatorial reactions and processes is compiled in
Table 2.
When an analytical instrument collects quantitative data from
a combinatorial experiment, the accuracy of determinations often
depends on the ability to provide an interference-free response.
The interferences can arise from a variety of sources and can
include chemical and environmental interferences. The ability to
provide accurate quantitative data improves with the increase of
the information content or dimensionality of the collected data
per combinatorial sample. Analytical instruments can be classified
according to the dimensionality of data that they provide
such as zero-, first-, second-, and higher order instruments. Such
classification of analytical instruments is well accepted 62 and can
be applied for description of capabilities of instruments for real
time monitoring and optimization of combinatorial reactions.
The classification principles are illustrated in Figure 3. A measurement
system that generates a single data point per combinatorial
sample is a zero-order instrument (see Figure 3A). First-order
measurement systems generate a string of multiple measurements
per combinatorial sample (see Figure 3B). Measurements provided
by the first-order measurement system are of the same
nature, for example, temporal, spectral, or sensor array responses.
Second-order measurement systems generate a matrix of an
instrument response upon the change of two independent types
of variables per sample (see Figure 3C). Depending on the particular
need in the combinatorial screening, higher-order measurement
systems are also possible. 63
Examples of performance of zero-, first-, and second-order
instruments in combinatorial screening of materials are presented
in Figure 4. A zero-order measurement approach is
illustrated in Figure 4A and B where abrasion resistance of
organic protective coatings was determined from measurements
of scattered light from each coating in a 48-element array. 34 A
simple zero-order measurement approach was useful because it
provided the required information about the end-use performance
of the protective coatings after an abrasion test (see
Figure 4A). Measurements of the abrasion-induced increase in
the amount of light scatter were performed at a single wavelength
as shown in Figure 4B. A single-wavelength measurement was
adequate for the correlation between the high-throughput and
traditional evaluation of abrasion resistance of coatings. 34
A first-order measurement approach is illustrated in Figure 4C
and D where measurements of fluorescence spectra of solid
582 dx.doi.org/10.1021/co200007w |ACS Comb. Sci. 2011, 13, 579–633