Research On The Optimization Method Of Oligonucleotide Synthesis And Its Implementation

With the accomplishment of the sequencing stage of the Human Genome Project (HGP), hoOw to analyze these data is the most important problem for all the biologists. Genechip is the cross-link between biotechnology and microelectronical technology, which has the advantage of high efficiency. Large scales of information can be attained by the use of genechip, so it is usually used to analyze the gene data. Probe fabrication is the key part of genechip and is directly related with the quality of the chip results and the following data analysis. Based on the in situ synthesis by molecular stamping method and the conditional control of the PCR chip hybridization, in this paper, a high-throughput multiple-probe synthesizer has been designed with the corresponding software. What's more, the system is linked with the synthesizer of the "mosaic" genechip and makes the synthesis half-automatization.The probe synthesizer is made to solve the problems which lie in the DNA synthesizer such as the high cost and long synthesis time. Using the theory of the combinational chemistry, we have made the problem above almost solved. In addition, we can simultaneously synthesize many kinds of compound probes by different combinations of the carriers. This method can probably deduce the cost of large number of DNA probes, and the genechip can be used more comprehensively.In this paper, a method of oligonucleotide synthesis optimization is proposed on the basis of the synthesizer. We use the cluster and other statistical methods to compress the synthesis of the same bases in the layers nearby. Thus we reduce thenumber of processes needed for DNA synthesis, to reduce the synthesis cycles, then to increase the efficiency of the DNA synthesis. Simultaneously, we use this method in the "mosaic" genechip fabrication and the result is satisfying.Finally we develop the software named OSS 1.0 which can provide genechip arraying, synthesis optimization documents and the linkage with the probe synthesizer. Then we realize the optimization design of the synthesis process.