Soft matter on-a-chip: Nanofluidics for single molecule DNA analysis and manipulation

纳米流体器件是在芯片上蚀刻的充满流体的通道网络，尺寸为1-100nm。具有如此小尺寸的设备可能具有与宏观世界类似物截然不同的特性，特别是操纵和分析单个分子的能力。PI的研究项目的核心——无论是纯的还是应用的——是使用纳米流体装置来操纵和分析DNA的单分子。DNA对生物学具有重要的基础意义，它本身就是一种重要的纳米结构材料，也是理解约束下聚电解质物理的模型系统。PI的基础研究计划的目标是创造新的知识（新的缩放定律，探索新的现象），同时将基础科学转化为新的设备概念。该应用组件利用纳米流体技术来解决生物医学中的紧迫问题。当DNA被挤进一个小的“纳米管”（例如使用高压）时，分子会伸展开来，沿着通道展开基因组。PI开发了一种新的“融化映射”方法来分析展开的DNA。延长的DNA通过化学和热变性部分融化，导致沿分子双链和单链区域共存。这种融化模式与序列有关。通过使用从熔化区域分离的染料，局部熔化模式可以光学地观察到暗区和亮区交替的“条形码”。长期目标是利用这种条形码技术创建全基因组图谱，以帮助测序、大规模结构变异的研究以及作为单细胞基因组分析的工具。

Nanofluidic devices are networks of fluid-filled channels etched on a chip with dimensions on order of 1-100nm. Devices with such small dimensions can have radically different properties than their macro world analogs, in particular the ability to manipulate and analyze single molecules. The core of the PI's research program-both pure and applied-is the use of nanofluidic devices for the manipulation and analysis of single molecules of DNA. DNA is of fundamental importance to biology, an important nanoscale structural material in its own right and a model system for understanding the physics of polyelectrolytes in confinement. The goal of the PI's fundamental research program is to create new knowledge (new scaling laws, explore new phenomena) while translating the basic science into new device concepts. The applied component makes use of nanofluidic technology to tackle immediate problems in biomedicine. When DNA is squeezed into a small 'nanopipe' (e.g. using high pressure) the molecule will stretch out, unscrolling the genome along the channel. The PI has developed a new 'melting mapping' approach for analyzing the unscrolled DNA. The extended DNA is partially melted via chemical and thermal denaturation, resulting in the co-existence of double stranded and single stranded regions along the molecule. This melting pattern is sequence dependent. By using dyes which unbind from melted regions, the local melting pattern can be observed optically as a "bar-code" of alternating dark and bright regions. The long term goal is to use this barcoding technology to create maps of entire genome to aid in sequencing, the study of large-scale structural variation and as a tool for single cell genomic analysis.