Molecular Electronics Page 2 May 14, 2003

Molecular Electronics

Enma 465

May 14, 2003

By Charles Brooks Mark Hanna Chen Kung Jia Ni Molecular Electronics Page 2 May 14, 2003

Introduction

Molecular electronics is a field emerging around the premise that is a possible to build individual molecules that can perform functions identical to those of the key components of today’s microcircuits. Current technologies used in microelectronics are approaching a limit to become smaller. Thus researchers are trying to develop more sophisticated forms of microelectronics or maybe “nano”-electronics. The areas of interest overlap with biotechnology, which includes DNA and cellular computing.

Why are people so fascinated with molecular electronics and why do researchers want to develop this form of technology when the modern technology of a silicon- integrated circuit can double its computing speed every 18 to 24 months? Why form molecular electronics when engineers can now put on a sliver of silicon of just a few square centimeters some 100 million transistors? The reason behind forming molecular electronics is because the world has a demand for smaller, faster, and just plain better technologies than we have. These several million transistors on centimeter square silicon are still far larger than molecular-scale devices would be. “To put the size differential in perspective, if the conventional transistor were scaled up so that it occupied the printed page you are reading, a molecular device would be the period at the end of this sentence.”

(6). Researchers believe in a dozen years, when industry projections suggest that silicon transistors will have shrunk to about 120 nanometers in length, they will still be more than 60,000 times larger in area than molecular electronic devices (6). The most Molecular Electronics Page 3 May 14, 2003 important aspect of developing molecular electronics is because at some point, chip- fabrication specialists will find it economically infeasible to continue scaling down microelectronics. The phenomena such as stray signals on the chip, the need to dissipate the heat from so many closely packed devices, and the difficulty of creating the devices in the first place will halt or severely slow progress when even more transistors are packed onto a chip. Therefore molecular electronics promises a more economically feasible way to more capable microelectronics.

Many researchers around the world have started to combine biology and electronics in the formation of molecular electronics. Recent studies have shown that individual molecules can conduct and switch electric current and store information. In

July of 1999 an electronic switch consisting of a layer of several million molecules of an organic substance called rotaxane was developed by researches of Hewlett Packard and the University of California at Los Angeles. Another major breakthrough is in June

2002, Fuji Xerox biotechnology made a prototype transistor of DNA from salmon sperm.

Researchers successfully passed an electric current through the DNA-transistor (7). This demonstrates that the chain behaves in a similar fashion to semiconductors. The current is created by attaching three thin electrodes; two to the ends and the third to the middle of the DNA chain. During the test runs, the voltage of the middle electrode was altered to switch OFF and ON the transmission function of the DNA chain. The length of the transistor is just 10 nm, about one 10,000th the thickness of a human hair (7). Researchers of Fuji Xerox claims that within 10 years a commercialized super small chip made with

DNA transistors will be developed and a super computer will be built small enough to fit into the palm of the hand. Molecular Electronics Page 4 May 14, 2003

Self-assembly is the autonomous organization of components into patterns or structures without human intervention. Self-assembling processes are common throughout nature and technology. They involve components from the molecular scale

(crystals) to the planetary (weather systems) scale and many different kinds of interactions. The concept of self-assembly is used increasingly in many disciplines, with a different emphasis in each.

Living cells self assemble. The cell offers countless examples of functional self- assembly that stimulate the design of non-living systems. Self-assembly is one of the few practical strategies for making ensembles of nanostructures. It will therefore be an essential part of nanotechnology. Manufacturing electronics will benefit from applications of self-assembly. (4)

DNA in molecular electronics is a promising area because researchers believe that it can achieve super-high density memory and high sensitive detection technology. DNA has be studied and tested for decades within biology, thus researchers have past experience to aid in understanding the behavior of DNA’s structure and performance in new applications and environments.

Cellular computing is another promising area for the future of microelectronics.

Researchers know well that cells have much, with respect to function, in common with machines and computers while also being very compact and self-assembling. If the ability to harness the computing power of cells is gained, this also may have the potential to break the barrier of making smaller computing technologies. Molecular Electronics Page 5 May 14, 2003

Self-Assembly in Electronics

Self-assembly is the autonomous organization of components into patterns or structures without human intervention. Self-assembling processes are common throughout nature and technology. They involve components from the molecular scale

(crystals) to the planetary (weather systems) scale and many different kinds of interactions. The concept of self-assembly is used increasingly in many disciplines, with a different emphasis in each.

Living cells self assemble. The cell offers countless examples of functional self- assembly that stimulate the design of non-living systems. Self-assembly is one of the few practical strategies for making ensembles of nanostructures. It will therefore be an essential part of nanotechnology. Manufacturing electronics will benefit from applications of self assembly. (4)

Types of Self-Assembly

There are different kinds of self assembly: static and dynamic. Static self- assembly involves systems that are at global or local equilibrium and do not dissipate energy. For example, molecular crystals are formed by static self-assembly; so are most folded, globular proteins. In static self-assembly, formation of the ordered structure may require energy but once it is formed, it is stable.

In dynamic self-assembly the interactions responsible for the formation of structures or patterns between components only occur if the system is dissipating energy.

The patterns formed by competition between reaction and diffusion in oscillating Molecular Electronics Page 6 May 14, 2003 chemical reactions are simple examples; biological cells are much more complex ones.

The study of dynamic self-assembly is in its infancy.

Although much of current understanding of self-assembly comes from the examination of static systems, the greatest challenges, and opportunities, lie in studying dynamic systems. (4)

Present and Future Applications

Self-assembly is already a widely applied strategy in synthesis and fabrication.

Can one predict areas where self assembly will be used in the future? Perhaps, these are possibilities:

 Crystallization at All Scales. The formation of regular, crystalline lattices is a fundamental process in self-assembly, and is a method to convert ;100-nm particles into photonic materials; using micrometer-scale components may lead to new routes to microelectronic devices (6).

 Robotics and Manufacturing. Robots are indispensable to current systems for manufacturing. As components become smaller, following the trend in miniaturization through microfabrication to nanofabrication, conventional robotic methods will fail because of the difficulty in building robots that can economically manipulate component only micrometers in size. Self-assembly offers a new approach to the assembly of parts with nano and micrometer dimensions.

 Nanoscience and Technology. There are two approaches to the fabrication of nanosystems: bottom-up and top-down. Chemical synthesis is developing a range of methods for making nanostructures—colloids, nanotubes, and wires—to use in bottom-up approaches. Self-assembly offers a route for assembling these components into larger, functional ensembles.

 Microelectronics. The fabrication of microelectronic devices is based almost entirely on photolithography, an intrinsically two-dimensional technology. Another computer of great interest—the brain—is three-dimensional. There are no clear strategic paths from two-dimensional to three-dimensional technology (and, of course, no absolute certainty that three-dimensional microelectronic Molecular Electronics Page 7 May 14, 2003

devices will be useful, al-though the brain is certainly a three-dimensional system, and three dimensionality offers, in principle, the advantages of short interconnects and efficient use of volume). Self-assembly offers a possible route to three- dimensional microsystems. (4)

Forming 3-D Electrical Networks by Self Assembly

In one study, self-assembly of millimeter-scale polyhedra, with surfaces patterned with solder dots, wires, and light-emitting diodes, generated electrically functional, three- dimensional networks. The patterns of dots and wires controlled the structure of the networks formed; both parallel and serial connections were generated.

Most fabrication of microelectronic devices is carried out by photolithography and is intrinsically two-dimensional (2D). The 3D interconnections required in current devices are fabricated by the superposition of stacked, parallel planes and by their connection using perpendicular vias. This group demonstrates self-assembly as a strategy to form interconnections between electronic devices and prefabricated circuits, and to form 3D electrical circuits.

Previous uses of self-assembly to fabricate electronic devices include shape- directed fluidic self-assembly of light-emitting diodes (LEDs) on silicon substrates and coplanar integration of segmented integrated circuit (IC) devices into 2D “superchips” using capillary forces at the surface of a flotation liquid. This group demonstrates the formation of two classes of 3D electrical networks—parallel and serial— by self- assembly, as an early step toward a strategy for fabricating 3D microelectronic devices.

The basic unit in these assemblies is a polyhedron [a truncated Molecular Electronics Page 8 May 14, 2003 octahedron ( TO)], on whose faces electrical circuits are printed. In the present demonstrations, these circuits include LEDs to demonstrate electrical connectivity and trace the networks; in the future, they will include devices with more complex functionality (e.g., processors). The LEDs are wired to patterns of solder dots on adjacent faces of the polyhedron. The TOs are suspended in an approximately isodense liquid at a temperature above the melting point of the solder (m.p. ; 47°C), and allowed to tumble gently into contact with one another. The drops of molten solder fuse, and the minimization of their interfacial free energy generates the forces that assemble the TOs into regular structures. Processes based on capillary interactions between solder drops have been used previously to assemble electronic and patterned polyhedra. Their self- assembly into 3D structures include electrical networks (5).

Although self-assembly originated in the study of molecules, it is a strategy that is, in principle, applicable at all scales. We believe that some of the self-assembling systems that are most amenable to fundamental study, and that are also most readily applied, may involve components that are larger than molecules, interacting by forces that have not commonly been used in synthesis or fabrication. Self-assembly thus provides one solution to the fabrication of ordered aggregates from components with sizes from nanometers to micrometers; these components fall awkwardly between the sizes that can be manipulated by chemistry and those that can be manipulated by conventional manufacturing. This range of sizes will be important for the development of nanotechnology (and the expansion of microtechnology into areas other than microelectronics). It will also be an area in which understanding biological structures and processes is very important. Molecular Electronics Page 9 May 14, 2003

Because of its well-known behavior and its electrical properties, DNA is a perfect candidate to be used in molecular electronics. DNA has been the object of intense research mainly due to its importance in biology. It is absolutely critical to the majority of known life forms. It has very specific self-assembly properties and may be highly selectively processed. DNA also functions at room temperatures and is highly stable.

Furthermore, the processing of DNA has been occurring excessively through the biological sciences for many years. More recently, the electrical properties of DNA have been studied to determine ways to fashion circuit element from it.

Deoxyribonucleic acid, referred to as DNA, is composed of two chains of nucleotides. These chains exist in a double helical structure with hydrogen bonds connecting the nucleotides of one strand to the other. There are four base pairs that make up the nucleotides. These four are adenine, thymine, cytosine, and guanine. Each base has its compliment. Adenine is compliment to thymine as is cytosine to guanine. These nucleotides are able to be in any sequence. This gives DNA the ability to store data, such as hereditary information.

So far DNA as been the most successful biomimetic component used for self- assembly (1). DNA is an extremely fine model for self-assembly. Complimentary DNA chains have a very strong affinity to each other and for a predictable structure when associated (2). Molecular Electronics Page 10 May 14, 2003

There exists the possibility of using the electrical properties of the chemical bonds in DNA to use the molecule as a single electron transistor. Phosphorus bridges connect the nucleotides along a chain. These phosphorus bridges form tunnel junctions for a net charge. The single electron in the π bond that forms between the neighboring oxygens and the phosphorus resembles an electron in a double well potential. When another electron approaches this situation, it is unable to occupy the same lowest energy level due to the Pauli exclusion principle. This electron is able to tunnel through the junction because the energy barrier is low and narrow (3).

Figure 1: Schematic of two DNA nucleotides connected with a phosphorus bridge. Dark circles are carbon atoms, white oxygen atoms (3).

It is also possible to selectively process DNA with the use of enzymes.

Restriction enzymes are able to mask specific segments of DNA. Researchers possess the ability to coat DNA strands with metal. DNA bridges were constructed between two gold electrodes spaced about 15 micrometers apart. Specific sequences of DNA were prepared with disulfide ends to attach to the gold electrodes. The DNA was processed

(including hybridization) using enzymes (T4 polynucleotide kinse and T4 ligase) and Molecular Electronics Page 11 May 14, 2003 various chemicals. After the formation of the DNA bridge, the bridge is coated in silver ions by ion exchange in a silver nitrate solution (8).

In order to form a single electron tunneling transistor two strands of DNA must be used, a main strand and a gate strand. The end base of the gate strand is attached to its compliment in the middle of the main strand. They are coated in metal except for the connection between the main strand and gate strand and the neighboring phosphorus bridges. The metallic coated end of the gate strand should be attached to a gate electrode and the ends of the main strand should be connected to two other electrodes (3). The creation of the interconnects pose a major challenge. This proposed DNA structure could function as a single electron tunneling transistor. Figure 2 shows a schematic diagram of the DNA transistor and its traditional equivalent. Molecular Electronics Page 12 May 14, 2003

Figure 2: Schematic of DNA Set and equivalent circuit. The shaded rectangles represent single stranded DNA. The Ps are bridging phosphorus bonds and the white square is a base paired to its compliment through the H bond. Vg is gate voltage in both situations (3).

The primary challenge faced by the completed design and mass production of the

DNA transistor is how to place the DNA transistors on a chip and connect all the proper electrodes. This is one of the major limiting factors in the example mentioned earlier with the DNA transistor created by Fuji Xerox (7).

The challenge of connecting the electrodes to the DNA chains may be overcome by using the selectivity in the DNA chains and DNA-functionalized nanoparticles. Other researchers have self assembled gold nanometer-sized particles by coating the particles with specific DNA sequences (9). Figure 3 shows a larger gold particle connected to many smaller gold particles using DNA as the connector. Molecular Electronics Page 13 May 14, 2003

Figure 3: 8 and 31 nm gold nanoparticles connected using DNA (9)

Perhaps it is possible to use this technique to connect DNA transistors to each other in desired arrangements creating a precise 3-d arrangement of transistors and connectors.

Cellular Computing

One of the important divisions of molecular electronics is cellular computing.

Research into cellular computing is driven by the need for computer technology to continue to get smaller. This research attempts to find an answer to the problem of what happens when we reach the minimum size attainable with silicon technology. As with all aspects of molecular electronics, cellular computing looks to biology to try and find some of the answers about fabricating nanometer scale components.

Interest in cellular computing began in 1994, when Adleman demonstrated that

DNA molecules could be manipulated to perform a specific kind of mathematical computation. This breakthrough stimulated interest in the possibility of fabricating a Molecular Electronics Page 14 May 14, 2003

DNA based molecular computer. The challenge is to use the cells computing power to do what we want it to do, instead of what it does naturally.

There are two types of molecular computers, true molecular computers, and quasi-molecular computers. True molecular computers have completely self-contained processes. All of their computational operations, such as inputs, outputs, and state transitions, are controlled by internally driven chemical reactions and molecular motors.

These true molecular computers can carry out their operations with no external support.

The only known example of a true molecular computer is the DNA based living cell (10).

Living cells can be thought of as true molecular computers because they have all the components that make up this type of computer. Cells have inputs provided by receptors, which recognize specific molecular ligands and input their information. The internal state of the cell is determined by Intercellular Dissipative Structures, or IDS’s

(11). Examples of IDS’s are phosphoproteins, gradients of metabolite concentrations, and mechanical stresses inside the cell. All of these entities contribute to determine the internal state of the cell.

The primary goal of cellular computing is to use artificial true molecular computers as the basis for a new computer technology. This is very difficult, because true molecular computers do what they are programmed to do by their DNA. They are not easily manipulated into producing a different output. On the other hand, the quasi- molecular computer is much easier to manipulate, and serves as a better basis for research. The quasi-molecular computer depends on getting most of its input and output operations, and its state transitions from an outside source (10). In this case, the outside Molecular Electronics Page 15 May 14, 2003 source would be a human, or robot, which helps the quasi-molecular computer do the things it, can’t do on its own.

Adleman’s DNA based computing system is an example of a quasi-molecular computer. In his experiment, he manipulated about 1014 molecules of 20-mer DNA to get it to perform the mathematical calculation (12). This system is a quasi-molecular computer because he had to synthesize the 20-mer DNA sequences himself. He also ran splicing reactions, and separated and purified the DNA products using conventional molecular biological techniques. Without Adleman’s contribution to this process, the quasi-molecular computer would not function at all. This introduces the secondary goal of cellular computing; to fabricate more efficient quasi-molecular computers that can carry out a major part of the computation with a minimal amount of assistance.

The idea of cellular computing depends on using biological components to replace the function of similar man made ones. To understand how this can be done, it is important to understand the biology of a cell, and how it functions as a molecular computer. Furthermore, it is important to find which connections can be made between molecular components and modern computers. Cells carry current in the form of electrons, in chemicals, while human-made computers use wires and electron fluxes for this purpose. Cells use enzymes to turn on and off chemical reactions, as human made computers use transistors to switch on or off the flow of electrons.

Chemicals also provide the energy source for cells, similar to the external power supply for human-made computers. For information storage, cells use both sequence patterns of biopolymers, and dissipative concentration gradients, or IDS’s (10), while human-made computers use capacitors. Computational programs are stored in DNA in Molecular Electronics Page 16 May 14, 2003 cells, in the form of lexical, syntactic and semantic genes, compared to the human-made computer’s software.

Te fact that cells and human-made computers have these components that do the same functions shows that they are fairly similar. It is these similarities that cause cells to be considered true molecular computers. Ji proposes three characteristics that characterize the cell as a true molecular computer. The first, Molecularity, means that all of the parts of the cell responsible for input, output, and state transitions are thermally fluctuating molecules. These processes within the cell are dependent on thermal fluctuations to drive them (10).

The second is the existence of an internal energy source. All of the molecular motors within the cell are driven by the energy stored within the motors themselves in the form of conformons. Conformons are conformational strains in chains of DNA, which cause the chains charge balance to be upset, and a small voltage to be developed. The cell uses this relationship between mechanical and electrical energy as a form of energy storage. Conformons have been shown to store 500 – 2500 Kcal/mol of energy in DNA, as well as 40- 200 bits of information (13).

The third characteristic is computability. This is the capacity of the cell to process input information and perform computations based on the information. In cells this information usually comes from a set of instructions stored in the DNA. These three characteristics of true molecular computers depend on the existence of three other things to function. Intracellular Dissipative Structures, or IDS’s are necessary to connect the information stored in biopolymers to the cell. Conformons are necessary to store the Molecular Electronics Page 17 May 14, 2003 energy that drives the cells molecular motors. Finally, the cell needs a language to allow cells to communicate with each other and make computations as a group (10).

One of the hardest things for humans to emulate using computers is the precision of biological processes. This makes progress in cellular computing extremely difficult.

If this goal can be achieved, and we learn how to fabricate and use cells as true cellular computers, a whole new dimension of computing is possible. Even though progress in this field is slow, the potential is there for this research to lead to the development of an entirely new computer technology.

Molecular electronics are the focus point of researchers today on a better and smaller microelectronics. DNA and cellular computing are capable of performing functions identical to those of the key components of today’s microcircuits. The major obstacle to overcome by researchers is how to assemble DNA and cells to perform the functions needed in circuits. Self-assembly is a major key to DNA production in microelectronics and researchers have to figure out how to make use of the different types of self-assembly to further develop a better microelectronics. Cellular computing is another form of future microelectronics to make circuits smaller and contains more transistors. Therefore the key to future applications of microelectronics is molecular electronics. Molecular Electronics Page 18 May 14, 2003

References

1. Seeman, N. C. (1999) Trends Biotechnol. 17, 437-443

2. Seeman, N. C., Belcher, A. M. (2002) Proc. Nat. Acad. Sci. USA 99, 6451- 6455

3. E. Ben-Jacob, Z. Hermon, S. Caspi, “DNA Transistor and Quantum Bit Element: Realization of Nano-Biomolecular Logical Devices” (1999) Phys. Lett. A 263, 199

4. Whitesides, George M. and Bartosz Gryzybowski. “Self-Assembly at All Scales.” Science Vol 295, (2002): pages 2418-2421.

5. Gracias, David H., Joe Tien, Tricia L Breen, Carey Hsu, Geroge Whitesides. “Forming Electrical Networks in Three Dimensions by Self-Assembly.” Science Vol 289, (2000): pages 1170-1172.

6. Reed, Mark A. and Tour, James M. “Computing With Molecules.” Scientific American.com. June 2000.

7. Science and Technology of Wing. “DNA transistors.” Science & Technology in Japan. June 2002.

8. E. Braun, Y. Eichen, U. Sivan and G. Ben-Yoseph, “DNA-templeted assembly and electrode attachment of a silver wire” Nature 391 , 775 (1998).

9. Y. Cao, R. Jin, Z. Li, A. Ivanisevic, J. Nam, S. Park, A. Lazarides “Solution Assembly of DNA-Functionalized Nanoparticles”

10. Ji, Sungchul. “The Cell as the Smallest DNA Based Molecular Computer.” BioSystems. (1999): 52. 123-133.

11. Ji, Sungchul. “Biocybernetics: A Machine Teory of Biology.” Molecular Theories of Cell Life and Death. Rutgers University Press, New Brunswick, 1-237.

12. Adleman, L.M. “Molecular Computation of Solutions to Combinatorial Problems.” Science. (1994): 266. 1021-1024.

13. Ji, Sungchul. “Cell Language (Cellese): Implications for Biology, Linguistics, and Philosophy.