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Role of high-throughput characterization tools in combinatorial materials science

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INSTITUTE OF PHYSICS PUBLISHING MEASUREMENT SCIENCE AND TECHNOLOGY
Meas. Sci. Technol. 16 (2005) 14 doi:10.1088/0957-0233/16/1/001

Role of high-throughput characterization

tools in combinatorial materials science
Radislav A Potyrailo1 and Ichiro Takeuchi2
1
General Electric Company, Global Research Center, Biosciences, Combichemistry and
Characterization Technologies, One Research Circle, Niskayuna, NY 12309, USA
2
Department of Materials Science and Engineering, Center for Superconductivity Research,
University of Maryland, College Park, MD 20742, USA
E-mail: potyrailo@crd.ge.com and takeuchi@squid.umd.edu

Received 23 July 2004, in final form 22 October 2004

Published 16 December 2004
Online at stacks.iop.org/MST/16/1

Abstract
The process of combinatorial materials development couples parallel
production of large arrays of compositionally varying samples together with
measurements of their properties. The diverse spectrum of functionalities in
materials represents a significant challenge in high-throughput
characterization, often involving development of novel measurement
instrumentation. Among the publications in the field, the number of
publications related to measurement techniques and instrumentation in
combinatorial materials science was the second largest category (34%) after
materials synthesis (37%). This statistic underscores the critical role
characterization tools play in combinatorial materials science.
Keywords: physical properties, chemical properties, morphological
properties, mechanical properties, optical properties, electrical properties,
biological properties, thermal properties, combinatorial approach, materials
science, high-throughput characterization, automated measurement, novel
measurement instrumentation, materials array

Combinatorial materials science has enjoyed much success for
over a decade since the publication of the first paper in the field
by Xiang et al [1]. The process of combinatorial materials
development couples the capability for parallel production
of large arrays of diverse materials together with different
measurement techniques for various physical properties and
subsequent navigation in the collected data for identifying
lead materials compositions [26]. Examples of materials
developed at the combinatorial scale and validated on scaled-
up versions in practical applications include catalysts [711],
phosphors [12], formulated organic coatings [13] and sensing
polymers [14].
In a typical combinatorial materials discovery cycle
(illustrated in figure 1) the characterization tools are used
for rapid, high-throughput and automated assessment of
single or multiple properties of the large number of
samples fabricated together as a combinatorial library. A
representative list of materials properties includes chemical,
morphological, mechanical, optical, electrical, biological
and thermal properties. Some representative intrinsic and
performance properties of polymers and inorganic materials
which need to be evaluated in a high-throughput manner are
listed in table 1. There are quite a few properties which are
important for both the fields, but there are also many properties
which are unique to each category.
In any type of combinatorial experimentation, having
the appropriate characterization tool is critical. Without a
suitable high-efficiency screening technique, high-throughput
synthesis by itself does not provide the information about
materials properties. For example, when a two million
compound library was synthesized with only a 15 ng amount
of each compound [15], the small amount proved to be
impossible to analyse using available screening tools [16].
To address a large number of materials-specific properties, a
variety of high-throughput characterization tools are required.
Ideally, a characterization system for combinatorial materials
discovery should be capable of handling small samples with
minimal sample preparation requirements and should have
rapid turnaround using either serial or parallel measurements
of library elements during or after the synthesis reaction.
It should also have high precision and high accuracy in
measurements. In addition, data acquisition, instrument

0957-0233/05/010001+04$30.00 2005 IOP Publishing Ltd Printed in the UK 1

R A Potyrailo and I Takeuchi

Table 1. Examples of intrinsic and performance properties important for high-throughput evaluation.
Properties of polymeric materials Properties of inorganic materials
Composition Stoichiometry
Polarity Microstructure and crystallinity
Impurities Impurities and their distribution
Fluid barrier property Structural defects and grain boundaries
Weatherability Resistivity
Molecular weight Superconducting transition
Melt viscosity Mobility
Glass transition temperature Breakdown voltage
Melting temperature Dielectric properties
Hydrolytic stability Piezoelectricity
Crystallization rate Polarization
Microstructure Bandgap
Crystallite orientation Refractive index and other optical properties
Hardness Saturation magnetization
Ductility Coercive field
Elasticity Magnetostriction
Chemical and oxidation resistance Spin polarization
Flame resistance Luminescence and other emission properties
Refractive index, colour Catalytic properties
Birefringence Chemical sensing properties
Coefficient of thermal expansion Mechanical properties
Thermal conductivity Ductility
Electrical conductivity Thermal properties
Dielectric constant Coefficient of thermal expansion
Biocompatibility Chemical and oxidation resistance

in memory devices and tunable microwave devices utilizing

Parallel
the similar class of ferroelectric materials have entirely
synthesis
different sets of materials performance requirements, and thus
Planning of
two completely different screening techniques are required.
Measurement of Overall, the diverse spectrum of functionalities in materials
combinatorial
Database performance
experiments
system
(table 1) represents a significant challenge in high-throughput
screening, often involving development of novel measurement
instrumentation. This is in contrast to combinatorial chemistry
in life sciences, where the luminescent-tagging method is
Data Data
mining processing widely applicable to many experiments. In many ways,
availability of characterization tools determines the scope of
ones combinatorial materials studies.
Lead The importance of developing characterization and
materials measurement techniques is also evident from the review of the
number of publications in the areas of combinatorial chemistry
Figure 1. Discovery cycle of materials using combinatorial and combinatorial materials science. Figure 2 compares the
experimentation. relative numbers of publications in these areas obtained using
SciFinder search engine (peer-reviewed papers, books and
book chapters, conference papers, patents, patent applications
operation and communication among instruments within the and other literature citations) in preparation of this paper.
discovery cycle should be automated. Data analysis should The field of combinatorial chemistry as a whole has scored
be effective in handling large amounts of data utilizing either the total number of 8092 publications, while combinatorial
univariate or multivariate algorithms and should be capable of materials science, by itself a young field, has scored only
providing simple transfer functions for the property of interest. 822 publications. The per cent distribution of publications
Finally, the structure of data management should be clearly laid for each field is broken down into categories similar to those
out and well organized [17]. Good data management schemes shown in figure 1. These categories were generalized from
should lead to new opportunities in experimental designs, data a more detailed search of keywords. The other category
mining and development of algorithms to correlate data from included the remaining publications. Interestingly, the relative
different characterization tools [18]. number of publications related to measurement techniques and
In advanced functional materials, the required instrumentation in combinatorial materials experimentation
performance of a material can become very specific depending was the second largest (34%) after publications related to
on its application. This often means one has to design, develop materials synthesis (37%). This statistic illustrates the
and tailor screening techniques which are highly specialized importance of characterization tools in combinatorial materials
for individual applications. For instance, capacitor dielectrics science.

2
 Role of high-throughput characterization tools in combinatorial materials science
Combinatorial Combinatorial
Chemistry Materials Science
10 10 11
4 materials science can be compared with the history of Raman
4 spectroscopy as an analytical tool. There were many major
46 30
37
34
12
1 1
planning
synthesis
measurement techniques and instrumentation
data processing
data mining
other
Figure 2. Comparison of the relative numbers of publications in
various aspects of combinatorial chemistry and combinatorial
materials science (shown as per cent to total number of
publications). Indicated categories are generalized from more
detailed search keywords.
(This figure is in colour only in the electronic version)
Although it is evident that development of new high-
throughput measurement techniques is non-trivial, other
aspects of the combinatorial discovery cycle for new materials
can be just as challenging to establish. We admire the
vision of pioneering researchers who demonstrated individual
phases of the combinatorial cycle long before 1995. It has
been documented that parallel synthesis and simultaneous
performance testing of multiple formulations had been carried
out long before the end of the 20th century [19, 20].
Fabrication of composition gradient samples for determining
alloy phase diagrams was demonstrated in the mid-1960s
[21]. In 1970, Hanak published a paper titled The
Multiple-Sample Concept in materials research: Synthesis,
compositional analysis and testing of entire multicomponent
systems, in which he described various phases of the materials
screening approach [22]. Indeed, Hanak suggested combining
several key steps into a single materials-development flow
diagram, including (1) complete compositional mapping of a
multicomponent system in one experiment, (2) simple rapid
non-destructive all-inclusive chemical analysis, (3) testing
of properties by a scanning device and (4) computer data
processing in tabular, graphical and functional forms [22].
If Hanak had published his first combinatorial materials
development paper in 1970, why do we celebrate 10 years,
instead of 35 years of combinatorial research today? As
pointed out by Wilhelm Maier, Hanak was truly ahead of his
time [23]. Although Hanak showed the way, at that time, the
followers did not have adequate instrumentation and the rest of
the components of the combinatorial cycle shown in figure 1
to fully implement his idea. Indeed, automated loading and
measurements of multiple samples have been practicsed with
autosamplers for various types of analytical instruments only
since the early 1970s [24, 25]. Data processing of hundreds
of data points is only now a common practice in sensor arrays
[26, 27] and multivariate statistical process controls [28].
This is often the case in the history of science that it takes
several decades for a great concept to mature into a practical
reality and to become accepted as a valuable scientific method.
This is due to the lack of supporting infrastructure at the initial
stage of the idea. In this regard, the history of combinatorial
stumbling blocks on the road before Raman measurements
became a mainstream technique. The breakthroughs in this
field took place over several decades. Implementation of
lasers boosted the Raman signal intensity, and introduction of
Fourier transform measurements and multichannel detectors
for simultaneous acquisition of the entire Raman spectrum led
to the widespread use of the technique. Today, Raman analysis
is routinely used for detailed materials evaluation with reliable
materials library searches. This example of evolution and
acceptance of Raman-based characterization tools may serve
as an inspiration for those who are starting the development
of new scientific concepts such as combinatorial materials
science.
Combinatorial methods have become well accepted in
the scientific community and are gaining their acceptance in
academic programmes around the world [5, 19, 23, 29, 30].
In addition to the attractive aspects of combinatorial materials
science such as the speed and the high level of details of
screening of composition and process parameter spaces, it
is important to keep in mind the remaining challenges and
possible limitations of combinatorial techniques. For example,
as recently outlined [5, 17], performance of new synthetic,
testing and characterization tools may not necessarily be
compatible with that of existing counterparts; thus, care should
be taken to establish the desired correlations and understand
the sources of possible discrepancies. Also, a high degree
of control should be maintained over synthesis and analysis
of individual samples in the library in order not to introduce
uncontrolled yet critical parameters that can change across the
library.
New developments in combinatorial and high-throughput
methodologies should focus on both new instrumentation for
analysis of diverse materials properties and new mathematical
approaches for processing of large amounts of data [31]. The
collection of articles in this special issue of Measurement
Science and Technology on combinatorial materials science
[32] provides a snapshot and highlights of the current trend
and technology of combinatorial methods with an emphasis
on measurement and analysis instrumentation in materials
science. The advances in components miniaturization,
electronics, computers, sensor technologies and data analysis
will continue to provide new opportunities in the development
of novel high-throughput characterization techniques.
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