Hydrodynamic Chirality: A novel method for chiral separation and analysis

描述（由申请人提供）：在这个SBIR快速通道中，我们专注于一种新的手性化学工艺技术，该技术可以在几分钟内在一台仪器中实现基线分离，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，为手性化学处理节省了大量的成本和时间。简而言之，当放置在毛细管中并暴露在旋转电场（REF）中时，左手和右手手性分子随着电场旋转，并相对于其溶剂起纳米级螺旋桨的作用。由于它们的相反手性，它们沿着磁场旋转轴向相反方向推进，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，如高压液相色谱法、x射线晶体学和振动圆二色法，往往耗时、昂贵、保真度低，并且通常阻碍手性化学的广泛研究。这项基于流体动力学手性和物理原理的新技术有望创造出一种易于使用、价格便宜一个数量级的手性分析和分离台式仪器。随着越来越多的研究人员、公司和大学能够负担得起手性分析和分离，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普遍益处，FDA要求大多数新药具有对映特异性，这增加了对新的手性分离和分析技术的需求。在第一阶段，具体目标是：1)设计并建立一个坚固可靠的REF分离室，工作频率高达300MHz，电压为100V p-p；2)在极性和非极性溶剂中对至少两个手性分子进行99%纯度的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/天的吞吐量。我们将使用旋转电场、微流体和手性检测来实现手性分析和分离。一旦技术在第一阶段得到验证，第二阶段的具体目标是1)设计和构建板级集成分离组件；2)设计一个一次性分离室，在分析规模下，商品成本低于10美元；3)为非专家开发和集成具有高保真度和易用性的预测软件；4)证明至少100个手性分子在极性和非极性溶剂中的广泛适用性；5)在毫克尺度上展示基线分离。除了第一阶段的方法，我们将使用从头算、分子力学和分子动力学模拟来确定推进方向和速度。

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.