0 on the board until it satisfies either of the two conditions listed below:
1 i. one player succeeds to place three respective marks in a row horizontally/ vertically/diagonally; the player is the winner;
2 ii. all nine squares are filled; the game is a tie.
In 1840s, Charles Babbage invented an automaton that is capable of playing tic-tactoe. It was one the first games which has been electronically coded on computer. In 1952, A. S. Douglas developed this video game on the Electronic Delay Storage Automatic Calculator (EDSAC) at the University of Cambridge.
A group of researchers from Columbia University and the University of New Mexico designed an interactive molecular machine with series of wells which are filled with hairpin-shaped DNA strands [12]. These nano-device is capable of playing tic-tac-toe game but with restricted moves. The molecular device is named as molecular array of YES and ANDANDNOT gates, or MAYA. This system is four times more complex than any previously designed DNA computer and the most powerful demonstration of DNA computing till date. It is also the first interactive use of programmable DNA enzymes.
MAYA I, which has been designed in 2003, contains 3×3 wells corresponding to the nine squares of the tic-tac-toe grid. The automaton is made up with 2 YES gates, 2 AND gates, and 19 ANDANDNOT gates. The solution of each well contains a specific set of DNA logic gates. The wells are designed in such a way that the enzymes of all the gates can cleave the same substrate DNA strand. The cleaving operation needs the cofactor Mg2+ ions to initiate its activity. The addition of the cofactor ions to all wells starts the game. According to the design strategy of this molecular device, MAYA is playing first and the first move is in the center well of the nine wells. The move of MAYA can be recognized from the increase in fluorescence from the central well as the enzymes in this well have no stem-loop structure to control the enzyme activity. Hence, the enzyme starts to cleave the DNA substrate immediately. The human opponent can give any one of the other eight possible inputs (move) which are represented by specific oligonucleotides. In MAYA I, this choice is constrained to square 1 or 4 to simplify the programming. As the board is symmetric, the human opponent moves somewhere else, the board could be rotated to make it a move in either square 1 or 4. The input oligonucleotides have complementary sequences to the sequences of the stem-loops that control the DNA gates of each well.
Let us assume that the human opponent gives his /her move to square 1. The DNA strand representing this move is added to all of the nine wells. Next, MAYA signals its move by the increment in fluorescence of another well. Each well has all input strands which represent all the moves of the human opponent during the onward movement of the game. The input strands are processed by the set of gates in each well.
In 2006, the research group reports the next generation, i.e., MAYA II, which is unrestricted and displays both players’ moves in two different fluorescent colors [13]. It is quadruple the size of its predecessor, i.e., MAYA I. The more user-friendly version, MAYA II combines 128 logic gates, 32 input molecules, and 8 two-channel florescent outputs. The green color signals the move of the human opponent and red color indicates the move by the automaton. The input oligonucleotides not only encode the position of the move but also represent the order of the move. It is not a fast process; it takes about 30 minutes for game fluorescence to overcome background levels.
The researchers suggest that the automaton for any symmetrical game strategy can be encoded by 152 gates using 32 inputs and allowing for subsequent additional activation in already played wells. The later provision still needs to be worked out.
One obstacle to translating the tic-tac-toe logic circuit to a biomedical setting is that it can be played only once. If the inputs and substrates have bound and stay in the well, then there is no way in this closed system to start again. So, the researchers have done simulations of DNA oscillators and flip-flop devices in an open system, which would enable the gates to be reset as old inputs and products are washed away and new ones enter a reaction chamber. Unfortunately, as the DNA oligonucleotides are expensive, the cost of actually carrying out an experiment in a typical 50-ml reactor is extremely high.
2.5.4.2 Medical Application of the Concept of DNA Logic Gate
DNA logic gates are being used for medical applications. A microfluidic network of reaction chambers, linked by channels, can mimic capillaries connecting living cells. The design strategy of MAYA can replace conventional silicon-based computing technology in situations where the sample is fluidic in nature; for example, sample of blood or a body. This technology has been used to improve the quality of diagnostics of the West Nile virus. Joanne Macdonald, the virologist from Columbia University, suggested that with required modification these kinds of nano-machines can be implanted in the human body. It is capable to control insulin level for diabetic patients and detect the presence of cancer cells.
Using this technology, the researchers have developed a novel approach to drug delivery by molecular robot. Taking their cue from movement studies of spiders, Pei et al. [14] constructed a molecular assembly which can extended the random walks on two-dimensional surfaces but in random direction. The 4-nm-diameter molecular spider is built with streptavidin protein. This nano-device has four binding pockets for a chemical moiety biotin and the pockets are placed symmetrically. The legs of the proposed robot are constructed with biotin-labeled DNA oligonucleotides. Thus, the legs can be bound to the body of the “spider”. Three of the legs are built with deoxyribozymes. The “start strand”, i.e., the fourth leg takes the robot to the starting site. Trigger strand release the molecular spider from its starting site. It can diffuse through a flexible, gel-supported matrix coated with oligonucleotide substrates that is complementary to the DNA legs by binding to and cleaving substrate molecules. In principle, the cleaved substrate could be a medication released when a spider “walks” by. The research group monitored the spider’s progress by looking at the release of products from the matrix with surface plasmon resonance. They report that the spider’s diffusion rate and the rate at which spider let go of the matrix and float away can be controlled by changing the number of legs or the size of the active binding regions between the substrate and legs. In this technique the rate of product release is linear which is very useful for controlled drug delivery. In future, a molecular spider can be constructed in such a way that it can carry a drug by binding to a 2D surface, for example, cell membrane, and after finding the receptors the local environment will trigger the drug activation. The molecular nanorobotics is the emerging technology which can be broadly used in the medical domain. But this may take 100 years in the future.
2.6 Advantages and Limitations
The conventional silicon-based computing has extensively empowered human being in technological aspect. But because of few drawbacks, the traditional computation is approaching toward the limitations of its processing power and design strategy. These technical challenges include immense energy consumption, vast memory requirement and heat dissipation. For this reason, the contemporary era is proposing the concepts of unconventional computation among which DNA computing is one of the promising domains. The advantages of this emerging methodology of computation are as follows:
• Huge storage capacity: DNA molecules have huge information storage capacity. It requires a trillion times less space to store same amount of data than an existing storage media. Approximately, 215 million gigabytes of data can be stored in a single gram of DNA oligonucleotide and several copies of the DNA strand can also be synthesized.
• Massive parallelism and speed: The elementary operations using DNA strands are slow, but here the parallelism prevails. Because of the massive parallel processing capabilities of DNA molecules, 1018 processors working in parallel in an in vitro assay can be handled by DNA computation. Thus, DNA computer has the capability to perform more than 100,000 times the speed of existing super computer.
• Low energy consumption: DNA computer uses 1 joule of energy to perform 1019 operations; on the other hand, existing super computer consumes same amount of energy to perform 1010 operations which makes it 109 times less energy efficient.
Thus, DNA molecule