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

该奖项开发了一种新的生物细胞样系统，用于访问和处理分子数据系统中的信息。具体来说，研究人员将建立新的技术，使电子系统中的定制基因表达和执行分子形式的信息处理成为可能。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。在开发一种新的电驱动基因表达方法的过程中，该项目为构建综合混合系统提供了一条途径，该系统利用了电子学（尺寸、精度、控制）和分子成分（密度、并行性、效率）的优势，实现了新的计算应用。除了计算之外，该项目还具有实现表征和控制合成遗传系统的新方法的潜力，并对生命科学、生物工程和人类健康产生影响。技术目标包括1)电子可编程无细胞基因表达系统（“eChromatin”），该系统将自动动态采购分子信息系统内操作生化过程所需的生物试剂；2)处理以分子形式存储的信息的新方法，如DNA数据随机访问和基于内容的相似性搜索，使用新的CRISPR-Cas9寻址方案和纳米孔测序来快速和高度复用访问分子数据。eChromatin系统设计由一个可切换的电极阵列组成，该电极阵列位于具有独特DNA成分的流动细胞中，这些DNA成分可以通过电子暴露或隔离，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的数据访问策略与之前的DNA数据存储工作相比具有显着优势，包括1)通过消除PCR准备和循环时间减少解码时间，2)增加多工性，3)增加存储密度，以及4)由于用等温反应取代PCR加热和冷却步骤而提高能源效率。然后，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演示中。该奖项反映了美国国家科学基金会的法定使命，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.