AUTOMATIC MULTIPLE-PARALLEL DNA PROBE SYNTHESIZER

人类基因组计划需要快速合成大量的 聚合酶链式反应扩增寡核苷酸引物的筛选 人类DNA，并用作序列标记位点的探针。这项建议 涉及一种快速自动倍增系统的发明。 寡核苷酸的并行合成。在我们的系统中，一系列 顺序反应是平行进行的，具有适当和预先的反应。 将程序核苷酸添加到每个反应序列中，并带有试剂流 在不使用单独泵的情况下准确分配和分离， 对个别试剂进行有效分割，并采用积极的方法 通过系统移动小体积并用于置换一种试剂 与下一次定量，试剂用量保持在最小。 此外，最终的裂解产物将进行层析纯化 在线，并以干燥的形式交付。该系统的两个版本是 提议，一种使用传统的颗粒固相载体， 第二，基于新技术，使坚实的支架成为一种 多孔膜。用目前的设计，可以制造50个或更多的底漆 平行的。该系统将比现在更紧凑、更便宜 合成器，可以建立在微观或宏观尺度上。

The Human Genome Project requires the rapid synthesis of very large numbers of oligonucleotide primers for polymerase chain reaction amplification of human DNA, and for use as probes for sequence-tagged sites. This proposal relates to the invention of a system for the rapid automatic multiple- parallel synthesis of oligonucleotides. In our system, a series of sequential reactions are carried out in parallel, with a proper and pre- programmed nucleotide added to each reaction train, with reagent streams accurately apportioned and separated without the use of separate pumps, with individual reagents effectively segmented, with positive methods for moving small volumes through the system and for displacing one reagent quantitatively with the next, and with reagent volumes kept to a minimum. In addition, the final cleaved product will be purified chromatographically on-line and delivered in a dry form. Two versions of the system are proposed, one using a conventional particulate solid-phase support, the second based on new technology which allows the solid support to be a porous film. With the present design 50 or more primers can be made in parallel. The system will be more compact and cheaper than present synthesizers, and can be built on either a micro- or macro-scale.