Fluorescent Molecule Rotor for Blood Plasma Viscometry

描述（由申请人提供）：液体复苏领域的当前结果表明，血浆粘度数据可能成为严重失血后容量恢复和血液置换形式和类型决策过程的组成部分。为此，待施用的流体的粘度及其对循环血液的所得血浆粘度的影响至关重要。这些考虑尤其与常规血浆扩张剂的配制和人工血液置换液的新兴领域相关。迄今为止，血浆粘度一直是通过机械装置测量的，这些机械装置容易产生测量误差（高公差），耗时，需要相当大量的流体，并且需要仔细清洁。分子转子是一类新型的荧光分子，其显示出粘度依赖性的荧光量子产率，因此可以用来确定其环境的粘度。基于我们发表的研究结果，分子转子可以成功地用于探测离体血浆粘度。在这里，我们提出了荧光探针的发展优化血浆粘度测量。这种测量流体粘度的新技术将允许快速和低样本量测量血浆和血浆膨胀剂的粘度。一旦优化，粘度荧光传感器将被连接到一个固体光学表面，以产生关键和独特的组成部分，为发展固体结合的光学分子粘度计。我们预计，这种用于测量流体粘度的全新技术将在广泛的医疗诊断方法中具有应用，由于普遍基于机械/液压机械的现有方法的复杂性，到目前为止还不能考虑这种应用。此外，该技术具有应用于许多其他领域的潜力，在这些领域中，需要在工艺过程中直接实时监测粘度。在生物医学应用方面，所提出的技术的独特性在于，它解决了迄今为止生物医学粘度测量不切实际的所有问题。它使用小体积样品，其大小与微量红细胞压积测定所需的相同。它测量血浆粘度。它使用廉价的一次性样品管，因此不需要清洁粘度测量表面和机械校准。这是一项需要最少培训和人员的技术。这是一种新的测量方法，在一个廉价和实用的系统中实施，配置为产生血浆粘度的临床相关数据，已被实验证明是预测生存的关键。它允许以最少的资源部署测试大量人群。该技术允许将血浆粘度作为临床相关参数进行处理，并通过简单且明确的红细胞压积测定程序打开了新的医学视野。

DESCRIPTION (p rovided by applicant): Current results in the field of fluid resuscitation indicate that data on plasma viscosity may become an integral part of the decision making process on the form and type of volume restitution and blood replacement following severe blood losses. To this end, the viscosity of the fluid to be administered and its effect on the resulting plasma viscosity of the circulating blood is of paramount importance. These considerations are especially relevant to the formulation of conventional plasma expanders and the emergent field of artificial blood replacement fluids. To date, plasma viscosity has been measured by mechanical devices, which are subject to measurement errors (high tolerances), are time-consuming, requires a fairly large amount of fluid and require meticulous cleaning. Molecular rotors are a novel class of fluorescent molecules that show a viscosity-dependent fluorescence quantum yield and thus can be exploited to determine the viscosity of their environment. Based on our published findings, molecular rotors can be successfully used to probe blood plasma viscosity ex-vivo. Herein we propose the development of fluorescent probes optimized for blood plasma viscosity measurements. This new technology for measuring fluid viscosity will allow fast and low sample volume measurements of the viscosity of blood plasma and blood plasma expanders. Once optimized, the viscosity fluorosensors will be attached to a solid optical surface to generate the critical and unique component for the development of solid-bound optical molecular viscometers. We expect that this fundamentally new technology for measuring fluid viscosity will have applications in a broad range of medical diagnostic approaches, which to the present could not be contemplated because of the complexity of existing methods universally based on mechano/hydraulically based machinery. Furthermore, this technology has the potential to be applicable in many other fields where direct real-time monitoring of viscosity during a process is required. In terms of biomedical applications the uniqueness of the technology proposed is that it addresses all the issues that so far have biomedical viscosity measurements impractical. It utilizes small volume samples, of size identical to that necessary for microhematocrit determinations. It measures plasma viscosity. It uses inexpensive, disposable sample tubes, and therefore does not require cleaning of viscometric surfaces and mechanical calibration. It is a technology that requires minimal training and personnel. It is a new measuring method, implemented in an inexpensive and practical system, configured to yield clinically relevant data on plasma viscosity that has been experimentally demonstrated to be critical for predicting survival. It allows testing of large populations with minimal deployment of resources. This technology allows dealing with plasma viscosity as a clinically relevant parameter, and opens a new medical horizon by means of a procedure that is a simple and unequivocal as a hematocrit determination.