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Trapping and separating objects in free solution by exploiting conformation-dependent electrophoretic mobility

利用构象依赖性电泳迁移率捕获和分离自由溶液中的物体

基本信息

批准号：
1826788
负责人：
Patrick Underhill
金额：
$ 34.9万
依托单位：
Rensselaer Polytechnic Institute
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1826788&HistoricalAwards=false
关键词：
Trapping separating objects free solution

项目摘要

The molecular structure of DNA gives rise to its twisting, ladder-like, double helix structure. Charged chemical groups link along the length of the ladder, forming the backbone for the sequence of base pairs that encodes genetic material. The double helix is folded and looped to fit within a cell, and the folded shape is dependent upon the sequencing of base pairs. Both the charging and shape of DNA provide a means to isolate and identify DNA. The response of DNA to an electric field (electrophoresis) has enabled laboratory isolation, sequencing, and unlocked the genetic code. To enable more rapid diagnostics, isolation can be accelerated by using the response of DNA to flow through microchannels, which is highly sensitive to shape, and thus sequencing. This project will develop and validate the theory necessary to simultaneously use charge and flow to isolate biomarkers, such as specific DNA sequences and viruses. Charged objects have an electrophoretic mobility that depends on their conformation. Conformation of folded molecules, in turn, is influenced by flow. This project will use computational methods to explore the fundamentals for isolation of deformable charged molecules in flow fields. Straight channels will be used to study cases in which separation occurs by different residence time through the device. Cross-slot channels will be used to study cases in which some molecules are trapped at the center of the device. Experiments with double-stranded DNA will be performed with the best device designs as validation of the mechanism for deformable polymers. Rigid orientable rods can resist compressional forces from the flow and electric field, which leads to an additional mechanism for trapping and separation. Simulations of rods with different flexibilities (from very rigid to very flexible) will determine how stiff the rods must be for this other mechanism to be present. The project will train two graduate students and two undergraduates, and incorporate the research into courses and online interactive tools that highlight application of mathematical modeling to biological separations. The project is the first step in developing next generation diagnostics for rapid identification of biological markers in a portable, small, and rapid device. This project is co-funded by the Molecular Separations program in the Division of Chemical, Bioengineering, Environmental and Transport Systems, and the Chemical Measurement and Imaging program in the Division of Chemistry.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.

DNA的分子结构产生了它的扭曲，梯形，双螺旋结构。带电荷的化学基团沿着梯子的长度连接，形成编码遗传物质的碱基对序列的骨架。双螺旋被折叠并成环以适合于细胞内，并且折叠的形状取决于碱基对的测序。DNA的电荷和形状提供了分离和鉴定DNA的手段。DNA对电场的反应（电泳）使实验室分离，测序和解锁遗传密码成为可能。为了实现更快速的诊断，可以通过使用DNA对流过微通道的响应来加速分离，微通道对形状高度敏感，从而对测序高度敏感。该项目将开发和验证同时使用电荷和流动分离生物标志物（如特定DNA序列和病毒）所需的理论。带电物体的电泳迁移率取决于它们的构象。折叠分子的构象反过来又受到流动的影响。本计画将利用计算方法探讨流场中可变形带电分子的分离原理。直通道将用于研究通过器械的不同停留时间发生分离的情况。交叉槽通道将用于研究一些分子被困在装置中心的情况。将使用最佳装置设计进行双链DNA实验，以验证可变形聚合物的机制。刚性可定向杆可以抵抗来自流和电场的压缩力，这导致用于捕获和分离的附加机制。对具有不同柔性的杆（从非常刚性到非常柔性）的模拟将确定杆必须有多硬才能存在这种其他机制。该项目将培训两名研究生和两名本科生，并将研究纳入课程和在线互动工具，突出数学建模在生物分离中的应用。该项目是开发下一代诊断的第一步，用于在便携式，小型和快速设备中快速识别生物标记物。该项目由化学、生物工程、环境和运输系统部的分子分离项目和化学部的化学测量和成像项目共同资助。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。