R. Cava et al. Progress in Solid State Chemistry 30(2002)1-101 into materials design opening exciting opportunities. As indicated in Fig. 6, block copolymers can be viewed as model macromolecules for the behavior of protein structures. It is thus not surprising that in the recent past these synthetic chain mol ecules and their self-assembly behavior have found their way into studies of size and shape control of inorganic materials. For example it has recently been demon- strated that block copolymers can be used to control the growth(habit) of anisotropic inorganic crystals [41]. Furthermore, block copolymers have found their way into the design of silica-type mesostructures [42]opening pathways to the preparation of ceramic nano-objects with controlled shape, size, and composition [43] as well as to mesoporous materials 44, 451 In the past organic-inorganic interfaces have been stabilized primarily through non-covalent interactions. Copying a strategy of natural systems, an alternative approach is to actually incorporate parts of the organic molecules, e.g. synthetic polymer chains, into the inorganic structures. Properties can be anticipated for such composite materials that are vastly different from those of the parent organic as wel as inorganic precursor materials, thus offering enormous scientific and technological promise for new materials with unknown property profiles [46]. Taking polymers as the organic molecules the future potential of this approach lies in the versatility of the polymer chemistry as well as that of the solid-state chemistry (e.g. sol-gel chemistry) that can be exploited in the materials synthesis. Complex hierarchical structures integrating functionalities from organic as well as inorganic materials might thus become available opening a whole new field to be explored Looking at Fig. 6 it is apparent that natural growth phenomena often operate far from equilibrium. In contrast, most materials investigated by the solid state chemistry community today are obtained from processes leading to equilibrium or"close to equilibrium structures. This has to do with the fact that in natural systems active transport processes are involved in structure formation. As an example, organic tem- plates for inorganic crystal growth might change as a function of time leading to 矿唧■國 唧唧 diblocks √⑩皚亨翰 國自 Fig. 6. Complexity diagram for blocked macromolecules [40](Reprinted by permission of American Chemical Society, USA)
R.J. Cava et al. / Progress in Solid State Chemistry 30 (2002) 1–101 21 into materials design opening exciting opportunities. As indicated in Fig. 6, block copolymers can be viewed as model macromolecules for the behavior of protein structures. It is thus not surprising that in the recent past these synthetic chain molecules and their self-assembly behavior have found their way into studies of size and shape control of inorganic materials. For example it has recently been demonstrated that block copolymers can be used to control the growth (habit) of anisotropic inorganic crystals [41]. Furthermore, block copolymers have found their way into the design of silica-type mesostructures [42] opening pathways to the preparation of ceramic nano-objects with controlled shape, size, and composition [43] as well as to mesoporous materials [44,45]. In the past organic–inorganic interfaces have been stabilized primarily through non-covalent interactions. Copying a strategy of natural systems, an alternative approach is to actually incorporate parts of the organic molecules, e.g. synthetic polymer chains, into the inorganic structures. Properties can be anticipated for such composite materials that are vastly different from those of the parent organic as well as inorganic precursor materials, thus offering enormous scientific and technological promise for new materials with unknown property profiles [46]. Taking polymers as the organic molecules the future potential of this approach lies in the versatility of the polymer chemistry as well as that of the solid-state chemistry (e.g. sol–gel chemistry) that can be exploited in the materials synthesis. Complex hierarchical structures integrating functionalities from organic as well as inorganic materials might thus become available opening a whole new field to be explored. Looking at Fig. 6 it is apparent that natural growth phenomena often operate far from equilibrium. In contrast, most materials investigated by the solid state chemistry community today are obtained from processes leading to equilibrium or “close to” equilibrium structures. This has to do with the fact that in natural systems active transport processes are involved in structure formation. As an example, organic templates for inorganic crystal growth might change as a function of time leading to Fig. 6. Complexity diagram for blocked macromolecules[40] (Reprinted by permission of American Chemical Society, USA)
R. Cava et al. Progress in Solid State Chemistry 30(2002)1-101 structures difficult to reproduce in the synthetic world. While the study of phenomena like "oscillatory reactions" in chemistry or"self-repair"in biology are well estab- lished these concepts have not yet found entry into synthesis strategies in solid state chemistry. The potential benefits are tremendous looking at structural and functional control of solid-state materials from the living world While offering tremendous scientific and technological promise, the integration of organic as well as inorganic molecules to novel hybrid materials according to con- cepts derived from natural systems poses a number of challenges to the solid-state community. Through the reduction of structural features to the nanoscale, surfaces and interfaces become dominant factors in the property control, a phenomenon gener ally appreciated in nanoscience. The integration of macromolecules(natural as well as synthetic)also significantly increases the importance of dynamical features of such systems. The width of the motional mode spectrum of polymers covers many orders of magnitude. Thus, the importance of techniques like solid-state nuclear mag netic resonance(NMR)spectroscopy, that are able to measure structure, order and dynamics over a broad range of time and length scales are expected to increase [ 47] Finally, integration of multiple components with multiple interactions into hier archical structures often leads to synergistic effects and thus complex behavior. Tack ling the multidimensional parameter space of such complex systems with linear tech- niques is inadequate. Faster approaches as, e.g., provided by combinatorial chemistry, are promising and are expected to lead to significant contributions in the field 3.4.2. What can solid state chemistry do for biology? his section outlines opportunities for applying solid-state materials and approaches to problems that traditionally lie in basic and applied biology. These opportunities include those where the methods and expertise common in solid-state materials are important to addressing scientific problems in biological areas and also those where the properties of solid-state materials are important to biotechnologies 3.4.2.1. Biointerfacial science Many biomedical and sensor technologies require that a material reside in contact with a biological fluid. The complex interactions between man-made materials and components of biological fluids(which principally include proteins)often lead to unwanted interactions with detrimental effects in the particular application. One limitation to understanding these non-specific interactions of proteins with materials has been a lack of analytical methods that have the sensi- tivity and spatial resolution for characterizing the bio-materials interface. At the same time, many of these techniques are common in solid-state materials-indeed, many have been developed because of the needs in this field-and offer important opportunities to gain a fundamental understanding of the more complex surface used in biological environments. There is a substantial opportunity to apply the experimental analytical methods of solid-state materials to elucidate the principles of the bio-materials interface and then guide the design of these interfaces that have controlled properties. Research and development on this frontier is critical to the development of several technologies, including indwelling sensors, tissue engineer ing and electrical prosthetic devices
22 R.J. Cava et al. / Progress in Solid State Chemistry 30 (2002) 1–101 structures difficult to reproduce in the synthetic world. While the study of phenomena like “oscillatory reactions” in chemistry or “self-repair” in biology are well established these concepts have not yet found entry into synthesis strategies in solid state chemistry. The potential benefits are tremendous looking at structural and functional control of solid-state materials from the living world. While offering tremendous scientific and technological promise, the integration of organic as well as inorganic molecules to novel hybrid materials according to concepts derived from natural systems poses a number of challenges to the solid-state community. Through the reduction of structural features to the nanoscale, surfaces and interfaces become dominant factors in the property control, a phenomenon generally appreciated in nanoscience. The integration of macromolecules (natural as well as synthetic) also significantly increases the importance of dynamical features of such systems. The width of the motional mode spectrum of polymers covers many orders of magnitude. Thus, the importance of techniques like solid-state nuclear magnetic resonance (NMR) spectroscopy, that are able to measure structure, order and dynamics over a broad range of time and length scales are expected to increase [47]. Finally, integration of multiple components with multiple interactions into hierarchical structures often leads to synergistic effects and thus complex behavior. Tackling the multidimensional parameter space of such complex systems with linear techniques is inadequate. Faster approaches as, e.g., provided by combinatorial chemistry, are promising and are expected to lead to significant contributions in the field. 3.4.2. What can solid state chemistry do for biology? This section outlines opportunities for applying solid-state materials and approaches to problems that traditionally lie in basic and applied biology. These opportunities include those where the methods and expertise common in solid-state materials are important to addressing scientific problems in biological areas and also those where the properties of solid-state materials are important to biotechnologies. 3.4.2.1. Biointerfacial science Many biomedical and sensor technologies require that a material reside in contact with a biological fluid. The complex interactions between man-made materials and components of biological fluids (which principally include proteins) often lead to unwanted interactions with detrimental effects in the particular application. One limitation to understanding these non-specific interactions of proteins with materials has been a lack of analytical methods that have the sensitivity and spatial resolution for characterizing the bio–materials interface. At the same time, many of these techniques are common in solid-state materials—indeed, many have been developed because of the needs in this field—and offer important opportunities to gain a fundamental understanding of the more complex surfaces used in biological environments. There is a substantial opportunity to apply the experimental analytical methods of solid-state materials to elucidate the principles of the bio–materials interface and then guide the design of these interfaces that have controlled properties. Research and development on this frontier is critical to the development of several technologies, including indwelling sensors, tissue engineering and electrical prosthetic devices
R. Cava et al. Progress in Solid State Chemistry 30(2002)1-101 3.4.2.2. Transduction schemes in sensors Biosensors combine a molecular recog nition function-for selective binding to the target analyte-with a transduction func tion that translates binding events ultimately to an electrical output. The most important sensing strategies to date have used either fluorescent or radioisotopic labels to quantitate bound analyte. While these methods are sensitive and time-tested, they have not been easily reduced to microformat (or the analogous lab on a chip formats)that are important to several sensor applications. The hardware required for counting isotope decay and for imaging fluorescence(particularly in confocal mode) are not yet reducible to microformat scales. Indeed, there are a range of opportunities for applying other transduction schemes that more directly couple biological activity at a substrate with a physical activity within the substrate. Many of these strategies- including those that rely on mechanical, thermal, magnetic, plasmon coupling- require solid-state substrates that possess tailored properties. These applications re resent an emerging frontier theme in solid-state materials 3.4.2.3. Hybrid cell-based technologies An emerging theme in engineering is the development of cell-based microtechnologies, which seek to build devices that com- bine cellular and tissue components with conventional materials processes found in microfabrication. This recent interest is motivated by the realization that the combi- nation of man-made systems and biological systems, which each have unique charac teristics,could yield engineered devices with broad new capabilities. The develop- ment of cell-based sensors that monitor environments for pathogenic agents have now entered con ommercialization and represent the possibilities for cell-based engin- eering. In the near term, a central challenge in these programs is the development of a common framework for designing and building structures having both material and biological components. This framework must address the development of stra tegies to integrate the functions of engineered systems-which are based on firm physics and engineering, use inorganic and metallic materials, and are constructed with photolithography and microfabrication tools-and biological systems-which use soft materials in aqueous environments, rely on self-assembly for their construc tion, and where the design rules are in many cases incompletely understood. Again the scientific and technical expertise that are common in solid-state materials have a central role to play in this emerging field 3.4.2.4. Synergistic technologies What new things can these two do together that is not specifically based on either of the two? Up to this point, the major concern has been to define interdisciplinary efforts in which either solid state chemistry or biology takes the lead. However, in exploring this boundary, one must also consider activities that are truly synergistic. These are completely new research directions that are not well represented by paradigms in either of the traditional fields. The path for the establishment of new paradigms is difficult to predict. Moreover, it also can be hard to follow-it often requires some time and substantiation by historical per spective before a new avenue can be declared a paradigm. Two examples are pro- vided in an attempt to suggest the potential for true synergy between these fields Recently, Montemagno et al. [48 reported harnessing of the F1-ATPase motor
R.J. Cava et al. / Progress in Solid State Chemistry 30 (2002) 1–101 23 3.4.2.2. Transduction schemes in sensors Biosensors combine a molecular recognition function—for selective binding to the target analyte—with a transduction function that translates binding events ultimately to an electrical output. The most important sensing strategies to date have used either fluorescent or radioisotopic labels to quantitate bound analyte. While these methods are sensitive and time-tested, they have not been easily reduced to microformat (or the analogous lab on a chip formats) that are important to several sensor applications. The hardware required for counting isotope decay and for imaging fluorescence (particularly in confocal mode) are not yet reducible to microformat scales. Indeed, there are a range of opportunities for applying other transduction schemes that more directly couple biological activity at a substrate with a physical activity within the substrate. Many of these strategies— including those that rely on mechanical, thermal, magnetic, plasmon coupling— require solid-state substrates that possess tailored properties. These applications represent an emerging frontier theme in solid-state materials. 3.4.2.3. Hybrid cell-based technologies An emerging theme in engineering is the development of cell-based microtechnologies, which seek to build devices that combine cellular and tissue components with conventional materials processes found in microfabrication. This recent interest is motivated by the realization that the combination of man-made systems and biological systems, which each have unique characteristics, could yield engineered devices with broad new capabilities. The development of cell-based sensors that monitor environments for pathogenic agents have now entered commercialization and represent the possibilities for cell-based engineering. In the near term, a central challenge in these programs is the development of a common framework for designing and building structures having both materials and biological components. This framework must address the development of strategies to integrate the functions of engineered systems—which are based on firm physics and engineering, use inorganic and metallic materials, and are constructed with photolithography and microfabrication tools—and biological systems—which use soft materials in aqueous environments, rely on self-assembly for their construction, and where the design rules are in many cases incompletely understood. Again, the scientific and technical expertise that are common in solid-state materials have a central role to play in this emerging field. 3.4.2.4. Synergistic technologies What new things can these two areas do together that is not specifically based on either of the two? Up to this point, the major concern has been to define interdisciplinary efforts in which either solid state chemistry or biology takes the lead. However, in exploring this boundary, one must also consider activities that are truly synergistic. These are completely new research directions that are not well represented by paradigms in either of the traditional fields. The path for the establishment of new paradigms is difficult to predict. Moreover, it also can be hard to follow—it often requires some time and substantiation by historical perspective before a new avenue can be declared a paradigm. Two examples are provided in an attempt to suggest the potential for true synergy between these fields. Recently, Montemagno et al. [48] reported harnessing of the F1-ATPase motor
R. Cava et al. Progress in Solid State Chemistry 30(2002)1-101 found in biology to produce a new type of nano-motor(Fig. 7). By using nano-scale ography techniques to define anchor points for the F1-ATPase apparatus and by attaching nickel nanowires to the tops of the motor, this biological system could be integrated with these solid-state structures to produce a motor. Biological motors have well-defined modes by which they operate and are powered. Moreover, they are highly efficient. This motor exploits all of these features and extends operation to the motion of nanoscale structures. Rotation of the nanopropeller was initiated with 2 mM adenosine triphosphate and inhibited by sodium azide. This motor could generate ca. 100 pN of force and, over the course of hours it performed with an efficiency of about 80%. To manufacture at the nanometer scale, motors and machines are likely to be required. Biological motors offer efficiency at the right length scale yet require the introduction of other, nanostructured elements to display the types of new functions one could envision wanting Another attractive place to exploit the biological apparatus is in energ ion. Greenbaum et al. have illustrated a biophotovoltaic device in which photo syn- thetic reaction centers are exploited to generate a photovoltage [49]. This is accomplished via the long-distance charge separation inherent in the photosynthetic process. By attaching these structures to platinum-coated chips, a photovoltage of approximately one volt per molecule can be measured This hybrid structure suggests opportunities in energy conversion and in computing elements as well(Fig. 8) 3.5. Needed infrastructure Programs that merge solid state materials with biology require new types of infra- structures. Significantly, user facilities for fabricating structures that are based on conventional micro-fabrication and on biological materials and methods do not yet exist. This need can be met by commissioning ' dirty fabs,, which contain common tools for microfabrication, deposition, and processing and also allow cells, proteins Fig. 7. Nanoscale biological motor[48](Reprinted by permission from American Association for the Advancement of Science, USA)
24 R.J. Cava et al. / Progress in Solid State Chemistry 30 (2002) 1–101 found in biology to produce a new type of nano-motor (Fig. 7). By using nano-scale lithography techniques to define anchor points for the F1-ATPase apparatus and by attaching nickel nanowires to the tops of the motor, this biological system could be integrated with these solid-state structures to produce a motor. Biological motors have well-defined modes by which they operate and are powered. Moreover, they are highly efficient. This motor exploits all of these features and extends operation to the motion of nanoscale structures. Rotation of the nanopropeller was initiated with 2 mM adenosine triphosphate and inhibited by sodium azide. This motor could generate ca. 100 pN of force and, over the course of hours it performed with an efficiency of about 80%. To manufacture at the nanometer scale, motors and machines are likely to be required. Biological motors offer efficiency at the right length scale yet require the introduction of other, nanostructured elements to display the types of new functions one could envision wanting. Another attractive place to exploit the biological apparatus is in energy transduction. Greenbaum et al. have illustrated a biophotovoltaic device in which photo synthetic reaction centers are exploited to generate a photovoltage [49]. This is accomplished via the long-distance charge separation inherent in the photosynthetic process. By attaching these structures to platinum-coated chips, a photovoltage of approximately one volt per molecule can be measured. This hybrid structure suggests opportunities in energy conversion and in computing elements as well (Fig. 8). 3.5. Needed infrastructure Programs that merge solid state materials with biology require new types of infrastructures. Significantly, user facilities for fabricating structures that are based on conventional micro-fabrication and on biological materials and methods do not yet exist. This need can be met by commissioning ‘dirty fabs’, which contain common tools for microfabrication, deposition, and processing and also allow cells, proteins, Fig. 7. Nanoscale biological motor[48] (Reprinted by permission from American Association for the Advancement of Science, USA)
R. Cava et al. /Progress in Solid State Chemistry 30(2002)1-101 ( Fig 8. The orientation of individual PSI reaction centers can be determined by the measurement of the I-V curve (A) If a PSI is oriented parallel to the electric surface, a semiconductor-like I-v curve wi a bandgap of-1. 8 ev can be observed. (B),(C) If a PSI is anchored perpendicular up as in(B)or down are examples taken from PSIs anchored on a 2-mercaptoethanol treated gold surface. For illustration purposes, the size of the PSI reaction center is enlarged. It is possibly embedded among the surface molecules so that the negative charge COD groups tug equally at the two positively charged end groups [49]( Reprinted by permission from American Physical Society, USA) nonconventional organic and inorganic materials to be used. The facilities also experienced full-time staff members that can maintain the equipment and work with non-expert users on specific projects. This latter point is very significant; many of the users of a dirty fab will not have experience in microfabrication and will not choose to spend several months learning the techniques inherent in microfab rication. A second broad infrastructure need is to support the highly diverse multi- investigator teams that will be necessary to make significant progress in this field Programs could be modeled after the NSf programs for Institutional research efforts (e.g. NSEC, MRSEC, ERC). In practice, these research centers provide important collaborative environments and support to seed research programs that are then very competitive for more traditional forms of funding 3.6. Educational objectives Clearly there is substantial potential profit in the integration of research activities solid state chemistry and biology. As this represents a new type of activity for both of these communities, one must ask what new educational objectives does this call for? First and foremost, it calls for scientists who are expertly trained in this area. This training can only happen in an environment where students hear about
R.J. Cava et al. / Progress in Solid State Chemistry 30 (2002) 1–101 25 Fig. 8. The orientation of individual PSI reaction centers can be determined by the measurement of the I–V curve. (A) If a PSI is oriented parallel to the electric surface, a semiconductor-like I–V curve with a bandgap of 1.8 eV can be observed. (B),(C) If a PSI is anchored perpendicular [up as in (B) or down as in (C)] to the gold surface, a diode-like (current rectification) I–V curve can be observed. (A) and (B) are examples taken from PSIs anchored on a 2-mercaptoethanol treated gold surface. For illustration purposes, the size of the PSI reaction center is enlarged. It is possibly embedded among the surface molecules so that the negative charge COD groups tug equally at the two positively charged end groups [49] (Reprinted by permission from American Physical Society, USA). nonconventional organic and inorganic materials to be used. The facilities also require experienced full-time staff members that can maintain the equipment and work with non-expert users on specific projects. This latter point is very significant; many of the users of a dirty fab will not have experience in microfabrication and will not choose to spend several months learning the techniques inherent in microfabrication. A second broad infrastructure need is to support the highly diverse multiinvestigator teams that will be necessary to make significant progress in this field. Programs could be modeled after the NSF programs for Institutional research efforts (e.g. NSEC, MRSEC, ERC). In practice, these research centers provide important collaborative environments and support to seed research programs that are then very competitive for more traditional forms of funding. 3.6. Educational objectives Clearly there is substantial potential profit in the integration of research activities in solid state chemistry and biology. As this represents a new type of activity for both of these communities, one must ask what new educational objectives does this call for? First and foremost, it calls for scientists who are expertly trained in this area. This training can only happen in an environment where students hear about