protein memory(seminar report)

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PROTEIN BASED MEMORY STORAGE DEVICES 1 1. INTRODUCTION Since the dawn of time, man has tried to record important events and techniques for everyday life. At first, it was sufficient to paint on the family cave wall how one hunted. Then came people who invented spoken languages and the need arose to record what one was saying without hearing it firsthand. Therefore, years later, earlier scholars invented writing to convey what was being said. Pictures gave way to letters which represented spoken sounds. Eventually clay tablets gave way to parchment, which gave way to paper. Paper was, and still is, the main way people convey information. However, in the mid twentieth century computers began to come into general use. Computers have gone through their own evolution in storage media. In the forties, fifties, and sixties, everyone who took a computer course used punched cards to give the computer information and store data. In 1956, researchers at IBM developed the first disk storage system. This was called RAMAC (Random Access Method of Accounting and Control). Since the days of punch cards, computer manufacturers have strived to squeeze more data into smaller spaces. That mission has produced both competing and complementary data storage technology including electronic circuits, magnetic media like hard disks and tape, and Department of Electronics and Communication, LMCST

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Page 1: Protein memory(seminar report)

PROTEIN BASED MEMORY STORAGE DEVICES 1

1. INTRODUCTION

Since the dawn of time, man has tried to record important events and techniques

for everyday life. At first, it was sufficient to paint on the family cave wall how one

hunted. Then came people who invented spoken languages and the need arose to record

what one was saying without hearing it firsthand. Therefore, years later, earlier scholars

invented writing to convey what was being said. Pictures gave way to letters which

represented spoken sounds. Eventually clay tablets gave way to parchment, which gave

way to paper. Paper was, and still is, the main way people convey information.

However, in the mid twentieth century computers began to come into general use.

Computers have gone through their own evolution in storage media. In the forties, fifties,

and sixties, everyone who took a computer course used punched cards to give the

computer information and store data. In 1956, researchers at IBM developed the first disk

storage system. This was called RAMAC (Random Access Method of Accounting and

Control).

Since the days of punch cards, computer manufacturers have strived to squeeze

more data into smaller spaces. That mission has produced both competing and

complementary data storage technology including electronic circuits, magnetic media like

hard disks and tape, and optical media such as compact disks. Today, companies

constantly push the limits of these technologies to improve their speed, reliability, and

throughput -- all while reducing cost. The fastest and most expensive storage technology

today is based on electronic storage in a circuit such as a solid state "disk drive" or flash

RAM. This technology is getting faster and is able to store more information thanks to

improved circuit manufacturing techniques that shrink the sizes of the chip features. Plans

are underway for putting up to a gigabyte of data onto a single chip.

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 2

Magnetic storage technologies used for most computer hard disks are the most

common and provide the best value for fast access to a large storage space. At the low

end, disk drives cost as little as 25 cents per and provide access time to data in ten

milliseconds. Drives can be ganged to improve reliability or throughput in a Redundant

Array of Inexpensive Disks (RAID). Magnetic tape is somewhat slower than disk, but it is

significantly cheaper per megabyte. At the high end, manufacturers are starting to ship

tapes that hold 40 gigabytes of data. These can be arrayed together into a Redundant Array

of Inexpensive Tapes (RAIT), if the throughput needs to be increased beyond the

capability of one drive. For randomly accessible removable storage; manufacturers are

beginning to ship low-cost cartridges that combine the speed and random access of a hard

drive with the low cost of tape. These drives can store from 100 megabytes to more than

one gigabyte per cartridge.

Standard compact disks are also gaining a reputation as an incredibly cheap way of

delivering data to desktops. They are the cheapest distribution medium around when

purchased in large quantities ($1 per 650 megabyte disk). This explains why so much

software is sold on CD-ROM today. With desktop CD-ROM recorders, individuals are

able to publish their own CD-ROMs.

With existing methods fast approaching their limits, it is no wonder that a number

of new storage technologies are developing. Currently, researches are looking at protein-

based memory to compete with the speed of electronic memory, the reliability of magnetic

hard-disks, and the capacities of optical/magnetic storage. We contend that three-

dimensional optical memory devices made from bacteriorhodopsin utilizing the two

photon read and write-method is such a technology with which the future of memory lies.

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 3

2. PRESENT MEMORY STORAGE DEVICES

The demands made upon computers and computing devices are increasing each

year, speeds are increasing at an extremely fast clip. However, the RAM used in most

computers is the same type of memory used several years ago. The limits of making

RAM denser are being reached. Surprisingly, these limits may be economical rather

than physical. A decrease by a factor of two in size will increase the cost of

manufacturing of semiconductor pieces by a factor of 5.

Currently, RAM is available in modules called DIMMs and SIMMs .These

modules can be bought in various capacities from a few hundred kilobytes of RAM to

about 64 megabytes. Anything more is both expensive and rare. These modules are

generally 70ns; however 60ns and 100ns modules are available. The lower the

nanosecond rating, the more the module will cost. Currently, a 64MB DIMM costs over

$400. All DIMMs are 12cm by 3cm by 1cm or about 36 cubic centimeters. Whereas a 5

cubic centimeter block of bacteriorhodopsin studded polymer could theoretically store

512 gigabytes of information. When this comparison is made, the advantage becomes

quite clear. Also, these bacteriorhodopsin modules could also theoretically run 1000

times faster.

In response to the demand for faster, more compact, and more affordable

memory storage devices, several alternatives have appeared in recent years. Among the

most promising approaches include memory storage using protein-based memory.

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 4

3. PROTEIN-BASED MEMORY

There have been many methods and proteins researched for use in computer

applications in recent years. However, among the most promising approaches, the

main one is 3-Dimensional Optical RAM storage using the light sensitive protein

bacteriorhodopsin.

Bacteriorhodopsin is a protein found in the purple membranes of several species

of bacteria, most notably Halobacterium halobium. This particular bacterium lives in

salt marshes. Salt marshes have very high salinity and temperatures can reach 140

degrees Fahrenheit. Unlike most proteins, bacteriorhodopsin does not break down at

these high temperatures.

Early research in the field of protein-based memories yielded some serious

problems with using proteins for practical computer applications. Among the most

serious of the problems was the instability and unreliable nature of proteins, which are

subject to thermal and photochemical degradation, making room-temperature or higher-

temperature use impossible. Largely through trial and error, and thanks in part to

nature's own natural selection process, scientists stumbled upon a light-harvesting

protein that has certain properties which make it a prime candidate for computer

applications. While bacteriorhodopsin can be used in any number of schemes to store

memory, we will focus our attention on the use of bacteriorhodopsin in 3-Dimensional

Optical Memories.

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 5

4. DEVELOPMENT IN THE FIELD OF MOLECULAR

ELECTRONICS

There is a revolution fomenting in the semiconductor industry. It may take 30

years or more to reach perfection, but when it does the advance may be so great that

today's computers will be little more than calculators compared to what will come after.

The revolution is called molecular electronics, and its goal is to depose silicon as king

of the computer chip and put carbon in its place. The perpetrators are a few clever

chemists trying to use pigment, proteins, polymers, and other organic molecules to

carry out the same task that microscopic patterns of silicon and metal do now.

For years these researchers worked in secret, mainly at their blackboards,

plotting and planning. Now they are beginning to conduct small forays in the

laboratory, and their few successes to date lead them to believe they were on the right

track. "We have a long way to go before carbon-based electronics replace silicon-based

electronics, but we can see now that we hope to revolutionize computer design and

performance," said Robert R. Birge, a professor of chemistry, Carnegie-Mellon

University, Pittsburgh. "Now it's only a matter of time, hard work, and some luck

before molecular electronics start having a noticeable impact." Molecular electronics is

so named because it uses molecules to act as the "wires" and "switches" of computer

chips. Wires may someday be replaced by polymers that conduct electricity, such as

polyacetylene and polyphenylenesulphide. Another candidate might be organometallic

compounds such as porphyrins and pthalocyanines which also conduct electricity.

When crystallized, these flat molecules stack like pancakes, and metal ions in their

centers line up with one another to form a one-dimensional wire.

Many organic molecules can exist in two distinct stable states that differ in some

measurable property and are interconvertable.These could be switches of molecular

electronics. For example, bacteriorhodopsin, a bacterial pigment, exists in two optical

states: one state absorbs green light, the other orange. Shinning green light on the

green-absorbing state converts it into the orange state and vice versa. Birge and his

coworkers have developed high density memory drives using bacteriorhodopsin.

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 6

"Electron transport in photosynthesis one of the most important energy generating

systems in nature, is a real-world example of what we're trying to do," said Phil Seiden,

manager of molecular science, IBM, Yorkstown Heights, N.Y. Birge, who heads the

Center for Molecular Electronics at Carnegie-Mellon, said two factors are driving this

developing revolution, more speed and less space.

"Semiconductor chip designers are always trying to cram more electronic

components into a smaller space, mostly to make computers faster," he said. "And

they've been quite good at it so far, but they are going to run into trouble quite soon." A

few years ago, for example, engineers at IBM made history last year when they built a

memory chip with enough transistors to store a million bytes if information, the

megabyte. It came as no big surprise. Nor did it when they came out with a 16-megabyte

chip.

Chip designers have been cramming more transistors into less space since Jack

Kilby at Texas Instruments and Robert Noyce at Fairchild Semiconductor first showed

how to put multitudes on electronic components on a slab of silicon. But 16 megabytes

may be near the end of the road. As bits get smaller and loser together, "crosstalk"

between them tends to degrade their performance. If the components were pushed any

closer they would short circuit. Physical limits have triumphed over engineering. That is

when chemistry will have its day. Carbon, the element common to all forms of life, will

become the element of computers too. "That is when we see electronics based on

inorganic semiconductors, namely silicon and gallium arsenide, giving way to

electronics based on organic compounds," said Scott E. Rickert, associate professor of

macromolecular science, Case Western Reserve University, Cleveland, and head of the

school's Polymer Micro device Laboratory. "As a result," added Rickert, "we could see

memory chips store billions of bytes of information and computers that are thousands

times faster. The science of molecular electronics could revolutionize computer design."

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 7

5. WHY BACTERIORHODOPSIN?

Bacteriorhodopsin (BR), a photon-driven proton pump, is a transmebrane

protein found in the purple membrane of the archaeon, Halobacterium halobium. The

BR is organized with polyprenoid lipid chains in the hydrophobic moiety on a highly

ordered two-dimensional lattice in the membrane. Enormous interest has been

generated by application of the structural and dynamic properties of the BR protein in

bioelectronics devices. Embedding bacteriorhodopsin in membrane films is essential to

achieve functionality of such devices. Although some prototype devices have been

fabricated, instability of the membranes is acknowledged as a major impediment to the

development of BR-based devices. Whereas there has been much biotechnological

experimentation on the properties and functionalities of the BR protein, comparatively

little attention has been paid to the critically important supporting lipid matrices in

which BR functions. Archaeal membranes consist predominantly of isoprenoid chains

ether-linked to an alcohol such as glycerol. These isoprene structures are unique and are

not prone to decomposition at high temperatures. That isoprene molecular fossils have

been found in geologic Miocene deposits attests to the extreme durability and stability

of these structures. In viable organisms BR functions in high efficiency at temperatures

as high as 140˚C, in near-saturating concentrations of salt, and in highly acidic

environments. Specific lipids of the purple membrane are required for normal

bacteriorhodopsin structure, function, and photo cycle kinetics.At ambient

temperatures,the membranes are in a liquid crystalline state that provides optimal

functioning of the BR..Adaptations of the membrane lipids allow maintenance of the

liquid crystalline state even as the indigenous conditions change. Nevertheless, as a

consequence of light absorption, BR initiates a photo cycle through structurally

distinctive conformations, causing tractable optical and electronic properties of the

protein. The characteristics of the lipids in the membrane dictate the large-amplitude

motions of BR,and by consequence the broad utility of bR in bioelectronic devices.The

research to be developed under this topic would have military and civilian importance.

Some of the bionanotechnological applications that are anticipated include: ultra rapid

optical data acquisition with parallel processing capabilities and extreme high density

holographic 3-dimensional data and image storage.

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 8

6. BACTERIORHODOPSIN OPTICAL MEMORY

Following are the features of Bacteriorhodopsin Optical Memory:-

1. Purple membrane from Halobacterium Halobium

2. Bistable red/green switch

3. In protein coat at 77K, 107-108 cycles

4.10,000 molecules/bit

5. Switching time, 500 femtoseconds

6. Monolayer fabricated by self-assembly

7. Speed currently limited by laser addressing

Using the purple membrane from the bacterium Halobacterium Halobium, Prof.

Robert Birge and his group at Syracuse University have made a working optical

bistable switch, fabricated in a monolayer by self-assembly, that reliably stores data

with 10,000 molecules per bit. 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. 

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 9

6.1 THE STRUCTURE OF BACTERIORHODOPSIN

Bacteriorhodopsin - as all retinal proteins from Halo bacterium - folds into a

seven-Tran membrane helix topology with short interconnecting loops. The helices

(named A-G) are arranged in an arc-like structure and tightly surround a retinal

molecule that is covalently bound via a Schiff base to a conserved lysine (Lys-216) on

helix G. The cross-section of BR with residues important for proton transfer and the

probable path of the proton are shown in Fig.1. The 3D structure is also available.

Retinal separates a cytoplasmic from an extra cellular half channel that is lined by

amino acids crucial for efficient proton transport by BR . The Schiff base between

retinal and Lys-216 is located at the center of this channel. To allow vectorial proton

transport, de- and reprotonation of the Schiff base must occur from different sides of

the membrane. Thus, the accessibility of the Schiff base for Asp-96 and Asp-85 must

be switched during the catalytic cycle. The geometry of the retinal, the protonation state

of the Schiff base, and its precise electrostatic interaction with the surrounding charges

and dipoles tune the absorption maximum to fit its biological function. 

Fig. 1: The 3D structure of Bacteriorhodopsin

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 10

6.2 BACTERIORHODOPSIN PHOTOCYCLE

Fig 2:Bacteriorhopsin Photocycle

Bacteriorhodopsin comprises of 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. In response to light Bacteriorhodopsin “pumps”

proton across the membrane, transporting charged ions in and out of the cell.

Bacteriorhodopsin goes through different intermediates during the proton pumping

cycle. These stages have been labelled K, L, M, N and O, each one easily identifiable

because Bacteriorhodopsin changes colour during each stage of the process. The native

photo cycle has several spectroscopically unique steps, bR --> K <--> L <--> M1 --

>M2 <--> N <-->O, which occur in a roughly linear order The photo cycle of

bacteriorhodopsin or its cycle of molecular states depend on the luminous radiation that

it absorbs. The initial state known as bR evolves into state K under the effect of green

light. From there it spontaneously passes to state M then to state O (relaxation

transitions).

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 11

Exposure to red light from O state will make the structure of the bacterium

evolve to state P then spontaneously to state Q, which is a very stable state.

Some of the intermediates are stable at about 80K and some are stable at room

temperature, lending themselves to different types of RAM. Nevertheless, radiation

from blue light can take the molecule from state Q back to the initial state bR. Any two

long lasting states can be assigned the binary value 0 or 1, making it possible to store

information as a series of Bacteriorhodopsin molecules in one state or another.

Genetic engineering has been used to create bacteriorhodopsin mutants with enhanced

materials properties.

Three-dimensional optical memory storage offers significant promise for the

development of a new generation of ultra-high density RAMs. One of the keys to this

process lies in the ability of the protein to occupy and form cubic matrices in a polymer

gel, allowing for truly three-dimensional memory storage. The other major component

in the process lies in the use of photons to read and write data. As discussed earlier,

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).

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 12

6.3 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. While early efforts to make use of

this property were carried out at cryogenic temperatures (liquid nitrogen

temperatures), modern research has made use of the different states of

bacteriorhodopsin to carry out these operations at room-temperature.

Fig 3. Data Writing Technique

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).

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 13

The data writing technique proposed by Dr. Birge 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 photo cycle 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 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.

6.4 DATA READING TECHNIQUE

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.

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 14

Fig 4.Data Reading Technique

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.

6.5 DATA ERASING TECHNIQUE

To erase data; a brief pulse from a blue laser returns molecules in the Q state

back to the rest state. The blue light doesn't necessarily have to be a laser; you can

bulk-erase the cuvette by exposing it to an incandescent light with ultraviolet output.

6.6 REFRESHING THE MEMORY

In Protein memory the read/write operations use two additional parity bits to

guard against errors. A page of data can be read nondestructively about 5000

times.Each page is monitored by a counter and after 1024 reads, the page is refreshed

by a new write operation.

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 15

7. MERITS

Fig 5.Birge’s Memory cell

This is based on a protein that is inexpensive to produce in quantity.

.The system has the ability to operate over a wider range of temperatures than

the semiconductor memory.

The data is stable, i.e. the memory system’s power is turned off, the molecules

retain their information.

This is portable, i.e. we can remove small data cubes and ship GBs of data

around for storage or backups

Data can be stored for years without any refreshment.

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 16

8. APPLICATIONS

Most successful applications of bacteriorhodopsin have been in the

development of holographic and volumetric three- dimensional memories.

Other applications of Bacteriorhodopsin are:-

When nutrients get scarce, this Bacteriorhodopsin becomes a light-

converting

enzyme. It's a protein powerhouse that in times of famine flips back and forth

between purple and yellow colours. If controllable, this could be valuable

in building battery conserving and long lasting computer display panels.

Protein’s photoelectric properties could be used to manufacture photo detectors.

Bacteriorhodopsin could be used as light sensitive element in artificial

retinas.

German scientists have used holographic thin films of

bacteriorhodopsin to

make pattern-recognition systems with high sensitivity and diffraction-limited

performance.

Nano biotechnology based medical diagnostics may use this proteins in imaging

devices.

Molecules can potentially serve as computers switches because their atoms

are mobile and change position in a predictable way. By directing the atomic

motion two discrete states can be generated in a molecule, which can be used to

represent either 0 or 1. This results in reduction of size, that is, a bimolecular

computer in principle is one-twentieth of t h e size of the present day

computer.

bR has all desired properties for usage in associative memory applications.

Department of Electronics and Communication, LMCST

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9. RESEARCH DEVELOPMENT

Branched- photocycle memory is developed at the W.M. Keck Centre for

Molecular Electronics at Syracuse University. This memory stores from 7 to 10

gigabytes (GB) of data in a small 1 × 1 × 3-cm3 cuvette containing the protein in a

polymer matrix Data are stored by using a sequential pair of one-photon processes,

which allows the use of inexpensive diode lasers to store one bit into the long-lived Q

state. The read/write/erase process is fairly complicated. The 10-GB data cuvettes used

in the 3-D memory described above can withstand substantial gravitational forces and

are unaffected by high-intensity electromagnetic radiation and cosmic rays. They can

even be submerged under water for months without compromising the reliability of the

data. 3-D protein memory cuvettes are already being designed and optimized for

archival data storage in office environments. Many millions of dollars have been spent

on this research and development. We have learned a great deal in recent years about

proteins and its applications.

Department of Electronics and Communication, LMCST

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PROTEIN BASED MEMORY STORAGE DEVICES 18

10. CONCLUSION

Birge’s system, which he categorizes as a level-1 prototype (i.e., a proof of

concept), sits on a lab bench. He has received additional funding from the US Air force,

Syracuse University, and the W.M.Keck foundation to develop a level-2 prototype.

Such a prototype would fit and operate within a desktop personal computer. “We are a

year or two away from doing internal testing on a level-2 prototype”, says Birge.

“Within three or five years, we could have a level-3 beta-test prototype ready, which

would be a commercial product.”

Department of Electronics and Communication, LMCST

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REFERENCES

1. www.cem.msu.edu

2. www.ieee.org

3. www.wikipedia.com

4. Samuel Styne Protein-Based Three-Dimensional

Memory, American Scientist, pp.328-355, July-August

2002.

5. Fedrro McKenzie, A model with Protein Storage, Int. J. Quantum Chem.,

vol. 95, pp. 627–631, 2003.

6. D. A. Thompson and J. S. Best, “The future of magnetic storage technology,”

IBM J. Res. Develop., vol. 44, pp. 311–322, 2000.

7. Marques Da Silva,

“Bacteriorhodopsin as a photochromic retinal protein optical memories,” Chem. Rev.

vol.100, pp. 1755–1776, 2000.

Department of Electronics and Communication, LMCST