Introduction
Molecular BioElectronics, with its unique blend of molecular physics, chemistry, and biotechnology is being hailed as the next frontier for research and development of applications related to nanobiotechnology, biomolecular engineering, bioelectronic devices and molecular miniaturization. Exciting progress is being made towards elaborating the materials and sensors capable of optimal hardware efficiency and intelligence, such as hybrid protein/semiconductor electronic devices, protein- and DNA-based computers, 3-D storage systems of unlimited capacity, molecular level resolution microscopes and imaging devices, and self assembled sub-micron supramolecular aggregates for electronic applications. All these and many other high-tech products are becoming a reality.
The ability of molecules to serve as computer switches has been a major area of scientific research since the middle of the last century. Molecular switches, if these become a reality, will offer appreciable reduction in hardware size, since these are themselves very small (about 1/1000th the size of a semiconductor). One can then imagine of a biomolecular computer about 1/20th the size of present-day semiconductor-based computers. Small size and fast operation will account for the development of most modern computers.
Although still a distant dream, the use of a hybrid technology in which the molecules and semiconductors combine and share duty could be possible in near future. Such technology would appreciably improve the speed and reduce the size of computers. Scientists have already sharpened their skills and are now trying to apply their knowledge to bring out the very best in this area.
Several biological molecules are being considered for use in computers, but the bacterial protein-bacteriorhodopsin (bR) – has generated much interest among scientists. In the past few decades, much research was North America, Europe, and
Bacteriorhodopsin is the light-harvesting protein found in the membrane of a microorganism called Halo bacterium halobium. It is a 26~kDa transmembrane protein that acts as a light-driven proton pump in Halobacterium salinarum, converting light energy into a proton gradient. bR is the only protein constituent of the purple membrane (PM), a two-dimensional crystal lattice naturally present as part of the plasmic membrane of the bacterium. Vectorial proton translocation through membranes is a fundamental energy conversion process in biological cells. This bacterium grows in salt marshes where the salt concentration is roughly six times the salt concentration in seawater. When the oxygen becomes too low to sustain respiration, the purple membrane, where the bacteriorhodopsin, resides is grown. The protein , upon the absorption of light, pumps a proton across the membrane, generating a chemical and osmotic potential that serves as an alternative source of energy. In this fashion, the Halo bacterium can, when the need arises, switch over from respiration to photosynthesis; this is a very unique characteristic.
Survival in the harsh environment of the salt marsh, where temperatures exceed 150 degrees Fahrenheit for extended periods of time, requires a durable protein that resists thermal and photochemical degradation. Survival in such an environment implies that this protein can resist thermal and photochemical damages. Evolution and natural selection have provided scientists with a natural protein, which can survive environments so harsh that few semiconductor devices could survive in such conditions.
Among the major advantages of using bacteriorhodopsin for computer applications are:
- Long-term stability and resistance to thermal and photochemical degradation
- A cyclist (the number of times it can be photochemically cycled) which exceeds 106, a value considerably higher than most synthetic photochromic materials
- High quantum yields (efficient use of light) which permits the use of low light levels for switching/activating
- Wavelength-independent quantum yields
- High two-photon cross sections, permitting activation in the infrared and three-dimensional memory architectures
- Generation of a photoelectric signal upon photoconversion, permitting electronic state assignment
- Ability to form thin films or oriented polymer cubes containing bacteriorhodopsin with excellent optical properties
- The molecule switches in 500 femtoseconds--that's 1/2000 of a nanosecond, and the actual speed of the memory is currently limited by how fast you can steer a laser beam to the correct spot on the memory.
- Monolayer fabricated by self-assembly.
These properties can be selectively enhanced for specific applications by a number of methods, i.e. using different chemical additives, substituting different chromophores, genetically engineering the protein's amino acid structure, etc.
Bacteriorhodopsin is the basic unit of protein memory and is the key protein in halobacterial photosynthesis. It functions like a light-driven photopump. Under exposure to light it transports photons from photosynthesis to respiration, and converts light energy to chemical energy. The response of this molecule to light energy can be utilized to frame protein memories.
Upon absorption of light, it generates a chemical and osmotic potential that serves as energy source. It has the ability to form thin films that exhibit excellent optical characteristics and offer long-term stability. The protein generates photoelectric signals upon photoconversion and can be used as optical memory. Also, it can be prepared in mass quantities.
Interests in bacteriorhodopsin date back to the early seventies when Walther Stocknius, University of
Photocycle Of Bacteriorhodopsin
Bacteriorhodopsin comprises a light 
absorbing component known as ‘chromophore’ that absorbs light energy and triggers a series of complex internal structural changes to alter the protein’s optical and electrical characteristics. This phenomenon is known as photocycle (Fig1).
The initial resting state of the molecule is known as ‘bR’ state to the intermediate state ‘k’. Next ‘k’ relaxes, forms another intermediate state ‘M’ and then ‘O’. When this intermediate state is exposed to red light, ‘O’ converts to another intermediate state ‘p’, which then relaxes to a more stable state ‘Q’. Blue light converts ‘Q’ back to the initial state ‘bR’. Here the idea is to assign any two long-lasting states to the binary values of ‘0’ and ‘1’, to store the required information.
Many of the erstwhile memory devices based on bacteriorhodopsin could operate only at extreme cold temperatures of liquid nitrogen in past, 
where light-induced switching between ‘bR’ and the intermediate state ‘K’ could be controlled. These devices were much faster than conventional semiconductor-based devices, as these exhibited the speed of a few trillionths of a second. Today, most bacteriorhodopsin based devices function even at room temperature, switching between ‘bR’ and another intermediate stable state ‘M’.
3-Dimensional Optical Memories
Three-dimensional optical memory storage offers significant promise for the development of a next generation of ultra-high density RAMs. One of the keys to this process lies in the ability of the protein to occupy different three-dimensional shapes and form cubic matrices in a polymer gel, allowing for truly three-dimensional memory storage. Storage capacity in two-dimensional optical memories is limited to approximately 1/lambda2 (lambda = wavelength of 
light), which comes out to approximately 108 bits per square centimeter. Three-dimensional memories, however, can store data at approximately 1/lambda3, which yields densities of 1011 to 1013 bits per cubic centimeter. The memory storage scheme which we will focus on, proposed by Robert Birge in Computer (Nov. 1992), is designed to store up to 18 gigabytes within a data storage system with dimensions of 1.6 cm * 1.6 cm * 2 cm. Bear in mind, this memory capacity is well below the theoretical maximum limit of 512 gigabytes for the same volume (5-cm3).
If a number of bacteriorhodopsin molecules are arranged in a three-dimensional fashion, high-speed, high-density, low-cost memories with vast capacities that can handle large volumes of data can be realized. Such memories offer over 300-fold improvement in storage capacity over their two-dimensional counterparts. Read/Write operations on these can be performed with the help of colored lasers that are fixed at such points in the plane of the cube (Fig 2).
Such memory cubes must be extremely uniform in their composition and must be homogeneous to ensure good results, since excess or defect of molecules in one particular region tends to distort the stored information and render the memory cube useless. The entire process of data storage of retrieval can be carried out in a few milliseconds. The speed of these memories depends on the number of cubes operating in parallel.
Data Writing Technique
Bacteriorhodopsin, after being initially exposed to light (in our case a laser beam), will change to between photo isomers during the main photochemical event when it absorbs energy from a second laser beam. This process is known as sequential one-photon architecture, or two-photon absorption.
The process breaks down like this:
Upon initially being struck with light (a laser beam), the bacteriorhodopsin alters its structure from the bR native state to a form we will call the O state. After a second pulse of light, the O state then changes to a P form, which quickly reverts to a very stable Q state, which is stable for long periods of time (even up to several years).
The data writing technique involves the use of a three-dimensional data storage system. In this case, a cube of bacteriorhodopsin in a polymer gel is surrounded by two arrays of laser beams placed at 90-degree angles from each other. One array of lasers, all set to green (called "paging" beams), activates the photocycle of the protein in any selected square plane, or page, within the cube. After a few milliseconds, the number of intermediate O stages of bacteriorhodopsin reaches near maximum. Now the other set, or array, of lasers - this time of red beams - is fired.
The Write Process
The second array is programmed to strike only the region of the activated square where the data bits are to be written, switching molecules there to the P structure. The P intermediate then quickly relaxes to the highly stable Q state. We then assign the initially-excited state, the O state, to a binary value of 0, and the P and Q states are assigned a binary value of 1. This process is now analogous to the binary switching system, which is used, in existing semiconductor and magnetic memories. However, because the laser array can activate molecules in various places throughout the selected page or plane, multiple data locations (known as "addresses") can be written simultaneously - or in other words, in parallel.
Data Reading Technique
Retrieval of stored data is carried out in a manner similar to storing the information, except that a detector images the light passing through the memory cube (Fig 3) and senses 1’s and 0’s. Here the property of selective absorption of red light by the intermediate state ‘O’ is relied upon. The detector senses the luminescent power falling upon it and converts the variations of optical power into a correspondingly varying electric current.
The system for reading stored memory, either during processing or extraction of a result, relies on the selective absorption of red light by the O intermediate state of bacteriorhodopsin. To read multiple bits of data in parallel, we start just as we do in the writing process. First, the green paging beam is fired at the square of protein to be read. After two milliseconds (enough time for the maximum amount of O intermediates to appear), the entire red laser array is turned on at a very low intensity of red light. The molecules that are in the binary state 1 (P or Q intermediate states) do not absorb the red light, or change their states, as they have already been excited by the intense red light during the data writing stage.
However, the molecules, which started out in the binary state 0 (the O intermediate state), do absorb the low-intensity red beams. A detector then images (reads) the light passing through the cube of memory and records the location of the O and P or Q structures; or in terms of binary code, the detector reads 0's and 1's. The process is complete in approximately 10 milliseconds, a rate of 10 megabytes per second for each page of memory.
An associative memory device that builds on holographic properties of thin films of bacteriorhodopsin has been developed. Associative memories take images or data blocks as input, scan the entire memory independently of a central processor for data block that matches the input and return the closest match. Such holographic thin films allow multiple images to be stored in the same segment of memory, thereby permitting simultaneous analysis of large sets of data. However, holograms based on bacteriorhodopsin are erasable.
Protein Memory Cd
The process of making the protein cube has many different steps. First the bacteria’s DNA is splice and mutated to make the protein more efficient for use as a volumetric memory. Then, the bacteria must be grown in large batches and the protein extracted. Finally, the purified protein is put into the cube and used as a volumetric storage medium.
Two lasers read the cube as binary code. One laser is used to activate the protein in a section of the cube. The other laser is used to write or read binary information in the same section. The data is assigned as either a zero or a one. The computer as various pieces of information then analyzes the binary code
The Design And Construction Of A Genetic Toggle Switch
Advances in biology and medicine are making gene therapy an increasingly practical approach to the treatment of human diseases. However, the range of regulatory behaviors permitted by current gene-expression systems is limited to the up- or down-regulation of genes in response to a sustained small-molecule signal. Construction of a genetic toggle switch a bistable gene expression network in Esherichia coli. The toggle is possible, which exhibits two stable expression states and a nearly ideal switching threshold, is flipped between states using transient chemical or thermal induction. The generality of the toggle switch design suggests that it will be applicable in higher organisms. As a practical device, the genetic toggle switch has significant implications for gene therapy and biotechnology. In addition, the toggle switch is a flexible and addressable cellular memory unit. Thus, it forms the basis for programmable, synthetic gene regulatory networks.
Fringemaker The First Commercial System Based On Bacteriorhodopsin
The FringeMaker system is a holographic camera, which uses bacteriorhodopsin (bR) films as photowritable/photoerasable optical recording media. This system is designed for applications in non-destructive testing, vibration analysis and size measurement. To our knowledge this is the first commercialized optical system were bR-films are employed. The FringeMaker System is able to resolve deformations down to 5 nm (l/100) and operates in 20 frames/second. The camera head is dust proof sealed and internally damped for applications in an industrial environment. All control and display devices are mounted in a 19 rack, which comes with the FringeMaker system. The system can be applied without any specific knowledge on bR.
Hybrid Bacteriorhodopsin-Based Semiconductor Devices
Molecular electronic applications for bacteriorhodopsin (bR) have been primarily photonic in nature, from holographic and three-dimensional optical memories to spatial light modulators and associative processors. Newer applications employ the protein's photoelectric properties, consisting of the sub-picosecond photovoltaic effect and a millisecond photocurrent. These properties have been harnessed to produce prototype photovoltaic cells and fast photodetectors, as well as artificial retinas. More recently, efforts have been made to incorporate bR into microscale and nanoscale semiconductor devices, with the goal of utilizing its light-induced electrical signal to modulate the properties of the device. For example, a thin polymer film containing bacteriorhodopsin could be used as the gate in a field effect transistor. The artificial retina and the bR-gated FET represent a new hybrid technology, integrating bacteriorhodopsin with semiconductor-based devices. Ongoing research is aimed at development of bR-based hybrid technologies.
Optical Data Storage, Image Processing And Biosensing With Bacteriorhodopsin
Bacteriorhodopsin (bR) has been proven to be an effective media for a variety of engineering applications, such as optically addressable spatial light modulators, volumetric memories, optical image processing systems, optical sensors, optical correlators and biosensors. However, practical realization of such systems with a bR depends upon the specific characteristics of this material. In this report we present experimental results of the time evolution and intensity dependent characteristics of a bR in the gelatin film and liquid form. In particular we studied the spectral dependence of the optical density/refraction index modulation. The two-channel time evolution technique was used for biosensor applications, in which the response of the modified and non-modified bR is compared to retrieve the information. A holographic technique was used to investigate the exposure characteristics of photorefraction and recording versus storage time. Also the connection between the diffraction efficiency of the recorded grating and light induced scattering (noise) the parameters that are of primary importance for such applications as high-density memory systems and optical correlators was investigated.
Biocomputing:
The latest computer hardware and software also increasingly resemble the biological realm. There is steady progress in developing protein memories, DNA computers and bio-luminescent displays. Software engineers are increasingly incorporating biological metaphors into the creation of more efficient and robust programs. The latest anti-virus programs utilize pseudo-immunological processes that evolve new defenses in response to the latest computer viruses.
Biocomputing could be generally described as an amalgam of the study of computational aspects of biosystems and biological aspects of computational systems. It encompasses a broad range of subjects and cuts across a wide range of academic disciplines. It can be divide it into two broad areas - biologically motivated computing and computationally motivated biology.
Biologically Motivated Computing
Biologically motivated computing is the application of biological source ideas to computer science. It is fascinating to see how, following his Ph.D. thesis on the simulation of nerve action, four well-known electronic devices emerged: Schmitt Trigger, Emitter-Follower, Differential Amplifier and Heat Pipe. Biologically motivated computing continues to provide the inspiration for engineering designs - from neural nets, immune algorithms, computational ecologies and evolutionary algorithms to analogue VLSI and Langmuir-Blodgett films.
Dna Computing
Despite their respective complexities, biological and mathematical operations have some similarities:
- The very complex structure of a living being is the result of applying simple operations to initial information encoded in a DNA sequence.
- The result f(w) of applying a computable function to an argument w can be obtained by applying a combination of basic simple functions to w.
For the same reasons that DNA was presumably selected for living organisms as a genetic material, its stability and predictability in reactions, DNA strings can also be used to encode information for mathematical systems.
Conclusion:
DNA computing is less than two years old (November 11, 1994), and for this reason, it is too early for either great optimism of great pessimism. Early computers such as ENIAC filled entire rooms, and had to be programmed by punch cards. Since that time, computers have since become much smaller and easier to use. It is possible that DNA computers will become more common for solving very complex problems, and just as PCR and DNA sequencing were once manual tasks, DNA computers may also become automated.
In addition to the direct benefits of using DNA computers for performing complex computations, some of the operations of DNA computers already have, and perceivably more will be used in molecular and biochemical research.
Reference:-
Websites:
-http://www.cem.msu.edu/~cem181h/projects/96/memory/
-http://lsb.syr.edu/projects/protein/about.html.
-http://www.fourmilab.ch/autofile/www/section2_84_18.html
-http://anx12.bio.uci.edu/~hudel/br/
-http://faculty.washington.edu/tebrey/ebrey/bactrho.html
Magazines:-
-Scientific American (March 1995 issue)
-Electronics for you.
TO DOWN LOAD REPORT AND PPT
