Collaborative Research: FET: Medium: Biological production and enzymatic processing for defect-free, scalable nucleic-acid circuits

“化学中央处理器”的发展将使生物化学环境中的计算成为可能，这种计算可以从环境中感知，处理信息，并驱动物理响应。实现这一目标所必需的是快速、坚固和可组合的分子组件，这些组件可以用物理分子实现逻辑行为，就像电子组件已经成功地用于处理信息一样。DNA链置换(DSD)电路是一个很有吸引力的候选电路。尽管DSD电路前景看好，但其作为一种技术的广泛采用仍存在许多可察觉的障碍：(I)DSD电路速度慢且容易出错，(Ii)DSD电路元件的制备困难且不易缩放，(Iii)DSD电路元件即使在提纯时也包含缺陷，以及(Iv)测量和控制DSD电路元件的浓度是有问题的。最近在“无泄漏”DSD系统方面的突破见证了第一个障碍的倒塌。该项目包括对所有级别的学生进行培训的计划。调查人员正在解决广泛采用DSD电路技术的三个剩余障碍。研究团队正在结合坚固的核酸电路体系结构、生产长长、高保真单链DNA的方法、额外的酶方法和新的实验方案，以便同时解决所有四个已确定的障碍。该项目旨在证明生物放大的、酶法制备的DSD组件能够产生卓越的核酸逻辑电路，从而实现这项技术的全新应用。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The development of “chemical central processing units” will make possible computation in bio-chemical contexts that can sense from the environment, process information, and actuate a physical response. Necessary to this goal are fast, robust and composable molecular components that can implement logic behavior with physical molecules, much like electronic components have been successfully used to process information. One attractive candidate is DNA Strand Displacement (DSD) circuits. Despite the promise of DSD circuits, there are a number of perceived barriers to their widespread adoption as a technology: (i) DSD circuits are slow & error-prone, (ii) preparation of DSD circuit components is difficult and does not easily scale, (iii) DSD circuit components, even when purified, contain defects, and (iv) measuring & controlling the concentration of DSD circuit components is problematic. Recent breakthroughs in “leakless” DSD systems have seen the first barrier fall. The project includes plans for training students at all level.The investigators are addressing the three remaining barriers to widespread adoption of DSD circuit technology. The team of researchers is combining robust nucleic-acid circuit architectures, methods of producing long, high-fidelity single-stranded DNA, additional enzymatic methods, and new experimental protocols in order to simultaneously address all four of the identified barriers. The project intends to demonstrate that biologically amplified, enzymatically prepared DSD components lead to superior nucleic-acid logic circuits leading to entirely new applications of this technology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.