nmat1157 6/11/04 11:28 AM Page 429 REVIEW ARTICLE Combinatorial solid-state chemistry of inorganic materials Throughout history, scientists and engineers have relied on the slow and serendipitous trial-and-error process for discovering and developing new materials. In contrast, an emerging theme in modern materials science is the notion of intelligent design of materials. Pioneered by the pharmaceutical industry and adapted for the purposes of materials science and engineering, the combinatorial approach represents a watershed in the process of accelerated discovery, development and optimization of materials. To survey large compositional landscapes rapidly, thousands of compositionally varying samples may be synthesized, processed and screened in a single experiment. Recent developments have been aided by innovative rapid characterization tools, and by advanced materials synthesis techniques such as laser molecular beam epitaxy which can be used to perform parallel-processed design and control of materials down to the atomic scale. Here we review the fast-growing field of combinatorial materials science, with an emphasis on inorganic functional materials. HIDEOMI KOINUMA1 AND The scope of the approach is far-reaching,and it can 2 be used to address materials issues at different levels ICHIRO TAKEUCHI * in a wide spectrum of topics ranging from catalytic 1Materials and Structures Laboratory,Tokyo Institute of powders5,6 and polymers7 to electronic and Technology,4259 Nagatsuta,Midori-ku,Yokohoma 226-8503, biofunctional materials.In solid-state applications, Japan the concept and effectiveness of the approach have 2Department of Materials Science and Engineering,and Center for been demonstrated by successful discoveries of new Superconductivity Research,University of Maryland,College Park, compounds in key technological areas including Maryland 20742,USA optical,dielectric and magnetic materials4,8,9. *e-mail: [email protected] Although the roots of this approach can be traced back to early phase-mapping experiments10–13 in the The practice of materials synthesis is analogous to 1960s,recent developments were spearheaded by work cooking in the sense that many factors — such as raw at the Lawrence Berkeley National Laboratory in the materials,tools and recipes — must be carefully 1990s14.In addition to serving the immediate materials selected and optimized by ‘tasting’at various stages. needs of industry,combinatorial techniques can be used The conventional one-by-one method for arriving at a to tackle fundamental issues of materials physics and good product takes a lot of time and energy.To compete chemistry.Composition spread and phase-diagram successfully and claim priority with new products and mapping experiments (where an entire compositional recipes,one must be able to accelerate the pace of the phase diagram is mapped onto a single chip) have optimization process.Component miniaturization and proved to be highly effective in rapidly uncovering and integration have played key roles in technological delineating the complex composition–structure– innovation,and they have led to breakthroughs in property relationships of unknown materials systems. the electronics industry.In the past two decades,the Thin-film synthesis techniques incorporating pharmaceutical and DNA-sequencing industries have spatially varying or selective deposition can be used to witnessed the emergence of similar innovation in the create combinatorial libraries and composition form of combinatorial chemistry and high-throughput spreads.There have been great developments in this screening (see,for example,ref.1).These techniques area,and tools for lattice engineering at the are now being extended to the field of materials science subnanometre level,such as laser molecular beam and engineering2–4. epitaxy (LMBE),have been used to fabricate In the combinatorial approach,a large number of compositionally varying samples15.In particular, compounds with different compositions are techniques using controlled molecular-layer synthesized and characterized together in parallel. deposition to fabricate thin-film and junction device nature materials | VOL 3 | JULY 2004 | www.nature.com/naturematerials 429 © 2004 Nature Publishing Group nmat1157 6/11/04 11:28 AM Page 430 REVIEW ARTICLE a No Figure 1 Materials synthesis as a multistep process.a,The reaction coordinate of the generalized scheme of materials synthesis where a Yes Disposal desired product (P) is obtained from reactants (R).Energy (E ) can be P supplied in various forms.b,Merrifield synthesis can be viewed as a (4) Characterization process where steps (1) to (3) in a are integrated.Sequences of E (3) Isolation different reactants (R) are attached to the bead (B).c,Microchemistry. Energy Mediator Reactants and a medium (M) are mixed in microreactors.Steps (1) to Catalyst (4) take place in a continuous flow.d,Combinatorial chemistry is a R (2) Reaction parallel integration of Merrifield synthesis.e,Combinatorial solid-state (1) Reagent feed technology:solid formation is carried out in parallel in a spatially Time addressable library. General scheme of synthesis b R 2 throughput characterization.Making quick and R1 R1 accurate measurements of a specific physical property from small volumes of materials often represents a R R ∑R 1 2 1 considerable feat of instrumentation.Researchers are B B B B R1 R2 Rn rinse rinse rinse R taking on this challenge,which in some cases has R1 R1 1 R1 Polymer bead R2 R2 led to the invention of new measurement instruments. A prime example is the scanning microwave Merrifield synthesis: integration of steps (1) to (3) microscope,an ideal non-destructive tool for studying ferroelectric,dielectric and conducting materials18. c E Probe It is expected that new measurement tools will continue to emerge as important by-products of R 1 combinatorial materials research. R2 M EVOLUTION AND INTEGRATION OF SYNTHESIS STEPS Glass chip Ageneralized way of looking at the synthesis of any Michrochemistry: (continuous) integration of steps (1) to (4) material is that it follows these steps.(1) Constituents or reactants (R) are simultaneously mixed or sequentially Memory chip assembled together,often assisted by a medium (M, d B which can be a carrier gas or a solvent).(2) Energy (E) is supplied to the system using a thermal process or other R1 R means of excitation under different conditions 2 (pressure, p,time,t,and so on) so as to drive the reaction Polymer bead process.(3) Desired products (P) are identified and B separated from the medium and other by-products formed in the reaction.(4) Finally,the products are R 1 3 characterized: this is the crucial part of any synthesis R 2 2 exercise,and it provides the feedback to the whole cycle. 1 The reaction coordinate of this generalized procedure is Merrifield ab c schematically illustrated in Fig. 1a.In this manner,the entire product formation process may be considered to Combinatorial be a function of various reaction parameters: Combinatorial chemistry: parallel integration of Merrifield synthesis P=f (R,t,p,E,M…) (1) e Energy in the form of beam (electron, ion, laser) Masking or printing or In a conventional materials development process, vehicle (solvent) 4 this procedure is performed repeatedly in order to span 3 2 the input parameter space until a satisfactory product is 1 obtained.In homogeneous organic syntheses involving abcd solvents,step (3) is especially time- and energy- Combinatorial consuming. Combinatorial technology: parallel integration of solid-state materials synthesis In 1963,Merrifield invented a scheme to improve the efficiency of synthesis,which is particularly useful for sequentially bonded compounds19,20.In this technique,reaction sites (linkers) anchored onto resin libraries,as well as phase diagram chips,have been beads serve as miniature reactors,and they are exposed developed by Koinuma and colleagues at Tokyo to an alternating series of reactants and a rinsing solvent Institute of Technology16,17. (Fig. 1b).This procedure can be viewed as steps (1) to The most formidable task in the combinatorial (3) in Fig. 1a integrated as one process.By repeating this approach is to implement effective tools for high- procedure,peptides are synthesized from amino acids. 430 nature materials | VOL 3 | JULY 2004 | www.nature.com/naturematerials © 2004 Nature Publishing Group nmat1157 6/11/04 11:28 AM Page 431 REVIEW ARTICLE Figure 2 Increasing complexity a y b c z and evolution in the combinatorial thin-film y technology.a,The natural A x x composition spread technique y was introduced in the 1960s. x Varying combinations of three different elements (A,B and C) Cxy are obtained at different positions on a wafer.b,On a spatially B C addressable library,each site can be addressed as Cxy. 1st generation 2nd generation 3rd generation c,Concurrent atomic layer-by- Natural composition spreadSpatially addressable library Layer-by-layer controlled array layer deposition can be used to design an array of crystal ( 1965 ) (1994) (1998) structures where stacking of molecular layers is controlled at a nanometre level. Another embodiment of materials synthesis appropriate complementary tools (computers and procedure in which steps (1) to (4) are integrated in rapid characterization methods).Equipment available series is in the emerging field of microchemistry21, at the time was primitive in measurement and data- where microreactors in the form of trenches patterned handling speed and capabilities. on slide glasses are used to carry out