Integrated Nanosystem Combining Engineered Nanopore Devices and Hierarchical Model-Based Diagnosis Algorithms for Ultra-Rapid Biomolecule Analysis

目的：本研究的目标是建立一个纳米尺度的系统，实现对核酸和蛋白质等生物分子的超快速、高分辨率分析。该方法基于纳米孔设备制造、基于预测物理的诊断算法来控制设备中的生物分子运输，以及这些子系统的集成来展示具有比目前可能的更高分辨率的高速生物分子分析。智力价值：这项工作解决了开发核酸和蛋白质测序平台的挑战，实现了时间和成本的数量级节省。这对于改变目前对疾病遗传基础的理解至关重要，从而使医学和生物技术的许多领域发生革命性的变化。这项工作对器件制造和高性能操作的关键问题采取了综合的方法。它结合了晶片规模的工艺(基于先进的电子束和原子层沉积技术)来制造第一个可重复的工程纳米孔器件阵列，以及一个新的计算诊断平台，该平台结合了分层详细的模拟引擎和数学算法，以自适应地优化单核苷酸？纳米孔器件的性能。决议。更广泛的影响：该计划将通过培训5个工程和科学学科的3名研究生和9名本科生，并通过与国家实验室的合作，培养跨学科和多样化的科学和技术人才。其中三名本科生将从代表不足的少数族裔中招募，方法是积极与一个校园项目合作，为代表不足的少数族裔创造研究机会。该项目将为电路诊断、纳米制造和纳米系统方面的本科生、研究生和继续教育课程开发动手模块。

Objective:The objective of this research is to create a nanoscale system that achieves ultra-rapid, high-resolution analysis of biomolecules such as nucleic acids and proteins. The approach is based on a combination of nanopore device fabrication, predictive physics-based diagnostic algorithms to control biomolecule transport in the device, and integration of these subsystems to demonstrate high-speed biomolecule analysis with much higher resolution than currently possible. Intellectual Merit:This work addresses the challenge of developing nucleic acid and protein sequencing platforms that achieve orders-of-magnitude savings in time and cost. This is essential to transform current understanding of the genetic basis of disease and thereby revolutionize many areas of medicine and biotechnology. This work takes an integrated approach to the critical issues of device fabrication and high-performance operation. It combines a wafer-scale process (based on advanced electron-beam and atomic layer deposition techniques) to fabricate the first reproducible arrays of engineered nanopore devices, with a novel computational diagnosis platform that couples hierarchically detailed simulation engines and mathematical algorithms to adaptively refine the nanopore device performance for ?single-nucleotide? resolution. Broader Impact:This program will develop interdisciplinary and diverse science and technology manpower by training three graduate and nine undergraduate students across five engineering and science disciplines, enhanced by collaborations with national laboratories. Three of the undergraduate trainees will be recruited from underrepresented minorities by active collaboration with a campus program for creating research opportunities for underrepresented minorities. The project will develop hands-on modules for undergraduate, graduate, and continuing education courses in circuit diagnosis, nanofabrication, and nanosystems.