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

“化学中央处理单元”的发展将使生物化学背景下的计算成为可能，这些计算可以从环境中感知，处理信息，并启动物理反应。实现这一目标所必需的是快速、鲁棒和可组合的分子组件，它们可以用物理分子实现逻辑行为，就像电子组件已成功用于处理信息一样。一个有吸引力的候选者是DNA链置换（DSD）电路。尽管DSD电路有希望，但是对于其作为技术的广泛采用存在许多感知到的障碍：（i）DSD电路是缓慢的、容易出错的，（ii）DSD电路组件的制备是困难的并且不容易缩放，（iii）DSD电路组件即使在被纯化时也包含缺陷，以及（iv）测量和控制DSD电路组件的浓度是有问题的。最近在“无泄漏”DSD系统中的突破已经看到了第一个障碍的下降。该项目包括培训各级学生的计划。调查人员正在解决广泛采用DSD电路技术的三个剩余障碍。研究小组正在结合强大的核酸电路架构，生产长，高保真单链DNA的方法，额外的酶促方法和新的实验方案，以同时解决所有四个确定的障碍。该项目旨在证明，生物扩增，酶法制备的DSD组件导致上级核酸逻辑电路，导致这一技术的全新应用。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.