Hydrodynamic Chirality: A novel method for chiral separation and analysis

流体动力学手性：一种手性分离和分析的新方法

基本信息

批准号：
8445275
负责人：
Osman Kibar
金额：
$ 56.56万
依托单位：
DYNAMIC CONNECTIONS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8445275
关键词：
Adverse effects Agriculture Analytical Chemistry Antibodies Binding Blood capillaries Cells Chemicals Chemistry Chromatography Complement Computer software Coupling Crystallization Crystallography Custom Dependence Detection Electronics Feedback Frequencies Hand Handedness High Pressure Liquid Chromatography Industry Institution Lead Left Libraries Marketing Methods Microfluidics Miniaturization Modeling Molecular Motion Performance Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Phase Physics Preparation Process Recording of previous events Research Research Personnel Risk Rotation Running Sampling Savings Services Small Business Innovation Research Grant Solutions Solvents System Techniques Technology Testing Therapeutic Index Time Universities Vibrational Circular Dichroism Work capillary catalyst chiral molecule commercial application commercialization cost design drug development drug discovery electric field enantiomer flexibility improved innovation instrument milligram molecular dynamics molecular mechanics nanoscale novel polarized light prototype public health relevance real world application screening small molecule stereochemistry tool voltage

项目摘要

DESCRIPTION (provided by applicant): In this SBIR Fast Track we focus on a novel chiral chemistry process technology that enables baseline separation, identification of absolute stereochemistry and purity analysis, all in one instrument and within minutes. The technology offers significant cost and time savings in chiral chemistry processing through inexpensive components and predictive software. Briefly, when placed in a capillary and exposed to a Rotating Electric Field (REF), left and right-handed chiral molecules rotate with the field and act as nanoscale propellers with respect to their solvent. Due to their opposite handedness, they propel along the axis of field rotation in opposite directions, enabling both isolation and analysis, including absolute configuration determination. Current techniques for chiral analysis and isolation such as high pressure liquid chromatography, x-ray crystallography and vibrational circular dichromism are frequently time consuming, expensive, low fidelity and are generally hindrances to the widespread study of chiral chemistry. This proposed new technique, relying on hydrodynamic chirality and principles of physics, promises to enable the creation of an easy-to-use, order of magnitude less expensive, benchtop instrument for chiral analysis and isolation. With more researchers, companies and universities able to afford chiral analysis and isolation, the pace of chiral drug study, discovery and commercialization is bound to increase. The FDA, due to the generally proven benefits of single enanatiomer compounds, mandates that most new drugs be enantiospecific, increasing the need for new chiral separation and analysis techniques. In Phase I, the Specific Aims are to 1) Design and build a robust and reliable REF separation chamber operating at up to 300MHz and 100V p-p; 2) Demonstrate quantitatively, 99% pure enantiomeric separation and high fidelity absolute configuration determination of at least two chiral molecules in both polar and nonpolar solvents; and 3) Investigate design parameter tradeoffs including voltage and frequency dependence and throughput up to gram per day scale. We will use rotating electric fields, microfluidics and chiral detection to achieve chiral analysis and isolation. Once the technique is proven in Phase I, for Phase II the Specific Aims 1) Design & build a board- level-integrated separation assembly; 2) Design a disposable separation chamber with cost of goods less than $10 at analytical scale; 3) Develop and integrate predictive software with high fidelity and ease-of-use for non-experts; 4) Demonstrate broad applicability for at least 100 chiral molecules in polar and nonpolar solvents; and 5) Demonstrate baseline separation at milligram scale. In addition to Phase I methods, we will use ab initio, molecular mechanics and molecular dynamics simulations to determine propulsion direction and velocity.

描述（由申请人提供）：在本 SBIR 快速通道中，我们重点关注一种新颖的手性化学工艺技术，该技术能够在一台仪器中在几分钟内实现基线分离、绝对立体化学鉴定和纯度分析。该技术通过廉价的组件和预测软件，显着节省了手性化学处理的成本和时间。简而言之，当放置在毛细管中并暴露于旋转电场（REF）时，左手性和右手性手性分子随电场旋转，并相对于其溶剂充当纳米级推进器。由于它们的旋向相反，它们沿相反方向的场旋转轴推进，从而实现隔离和分析，包括绝对构型确定。目前的手性分析和分离技术，例如高压液相色谱、X射线晶体学和振动圆二色性通常耗时、昂贵、保真度低，并且通常阻碍手性化学的广泛研究。这项提出的新技术依赖于流体动力学手性和物理原理，有望创建一种易于使用、价格便宜的台式仪器，用于手性分析和分离。随着越来越多的研究人员、公司和大学能够承担手性分析和分离的费用，手性药物研究、发现和商业化的步伐必将加快。由于单一对映异构体化合物的优点已得到普遍证明，FDA 要求大多数新药必须具有对映异构体特异性，从而增加了对新手性分离和分析技术的需求。在第一阶段，具体目标是 1) 设计和建造一个坚固可靠的 REF 分离室，运行频率高达 300MHz 和 100V p-p； 2) 在极性和非极性溶剂中定量展示至少两个手性分子的 99% 纯对映体分离和高保真度绝对构型测定； 3) 研究设计参数权衡，包括电压和频率依赖性以及高达克/天规模的吞吐量。我们将利用旋转电场、微流控和手性检测来实现手性分析和分离。一旦该技术在第一阶段得到验证，第二阶段的具体目标 1) 设计和构建板级集成分离组件； 2) 设计一次性分离室，分析规模的商品成本低于 10 美元； 3）开发和集成高保真度且易于非专家使用的预测软件； 4) 展示至少100个手性分子在极性和非极性溶剂中的广泛适用性； 5) 展示毫克级的基线分离。除了第一阶段方法之外，我们还将使用从头算、分子力学和分子动力学模拟来确定推进方向和速度。