CCF: FET: Medium: A bio-electronic processor for molecular information systems

该奖项开发了一种新型的生物细胞样系统，用于访问和处理分子数据系统中的信息。具体来说，研究人员将建立新技术，使定制的基因表达在电子系统中，并进行分子形式的信息处理。该项目的目标是探索混合电子分子工程的新方法，利用分子机制，DNA测序技术和电子学的进展。在开发电驱动基因表达的新方法时，该项目提出了一种构建集成混合系统的途径，该系统利用了电子器件（尺寸，精度，控制）和分子组件（密度，并行性，效率）的优势，从而实现了新的计算应用。除了计算之外，该项目还可能实现表征和控制合成遗传系统的新方法，对生命科学，生物工程和人类健康产生影响。（“eChromatin”），其将自动化在分子信息系统内操作生化过程所需的生物试剂的动态来源;以及2）处理以分子形式存储的信息的新方法，例如使用新的CRISPR-Cas9寻址方案的DNA数据随机访问和基于内容的相似性搜索，以及用于快速和高度多路复用访问分子数据的纳米孔测序。 eChromatin系统设计由流动池中的可切换电极阵列组成，该流动池图案化有独特的DNA组分，这些DNA组分可以电子暴露或隔离，从而实现类似于天然染色质-DNA复合物重塑的动态基因表达。基于Cas9的数据访问策略被设计为在DNA数据存储中具有比先前工作显著的优势，包括1）通过消除PCR准备和循环时间来减少解码时间，2）增加的多路复用性，3）增加的存储密度，以及4）由于用等温反应代替PCR加热和冷却步骤而增加的能量效率。研究人员将把这些方法整合到大规模DNA数据池中的自动化端到端协议的演示中。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award develops a novel biological cell-like system for accessing and processing information in molecular data systems. Specifically, the investigators will build new technologies that enable customized gene expression in an electronic system and perform information processing in molecular form. The goals of the project explore new methods of hybrid electronic-molecular engineering that leverage progress in molecular mechanisms, DNA sequencing technology, and electronics. In developing a novel approach to electrically-actuated gene expression, the project presents a path towards building integrated hybrid systems that draw on the strengths of electronics (size, precision, control) and molecular components (density, parallelism, efficiency), enabling new computing applications. Beyond computing, the project has the potential to enable new methods of characterizing and controlling synthetic genetic systems with impact in the life sciences, bioengineering, and human health.Technical objectives include 1) an electronically programmable cell-free gene expression system (“eChromatin”) that will automate dynamic sourcing of biological reagents needed to operate biochemical processes within molecular information systems; and 2) new methods of processing information stored in molecular form, such as DNA data random access and content-based similarity search using a new CRISPR-Cas9 addressing scheme and nanopore sequencing for fast and highly multiplexed access of molecular data. The eChromatin system design consists of a switchable electrode array in a flow cell patterned with unique DNA components that can be electronically exposed or sequestered, enabling dynamic gene expression analogous to the remodeling of natural chromatin-DNA complexes. The Cas9-based data access strategy is designed to have significant advantages over previous work in DNA data storage, including 1) decreased time-to-decoding by eliminating PCR prep and cycle time, 2) increased multiplexability, 3) increased storage densities, and 4) increased energy efficiencies due to replacing PCR heating and cooling steps with isothermal reactions. The investigators will then integrate these approaches in a demonstration of automated end-to-end protocols within large-scale DNA data pools.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.