Feasibility study into the use of histotripsy for haemolysis for automated blood testing

为了在床旁血液分析中进行某些测定，血细胞的细胞膜必须是透明的。 破裂的过程称为溶血。传统上，这是使用强大的化学洗涤剂， 但这些化学物质会干扰血液分析，影响测试结果。该补助金的目的是 研究一种完全机械的溶血方法，使用超声诱导的空化， 称为组织摧毁术组织摧毁术涉及应用低占空比、高峰压力超声 脉冲到目标。它已被用于许多非侵入性治疗应用中， 其显示为机械地均质化组织而不引起加热。据我们所知，还没有人使用 用于溶血的组织破坏技术，它有可能实现高通量自动血液分析。 没有化学溶解的复杂影响的测试。组织摧毁术特别适合于微流体 血液分析，因为竞争性超声裂解技术使用微泡和/或未聚焦的 超声波束与微流体系统的受限体积和小尺寸不相容。 该项目将包括一个系统的发展，产生控制，高峰压力脉冲 使用申请人实验室中现有的高强度聚焦超声换能器。系统的能力， 将通过高分辨率超声成像验证是否产生空化，并通过溶血进行确认 动物的血液样本。超声脉冲幅度、频率和占空比将被优化以增强 裂解 该项目将与总部位于渥太华的Alere-Epocal合作进行，该公司是一家领先的 即时微流控血液检测成功完成可行性研究将导致长期 合作将基于histotripsy的裂解纳入Alere-Epocal产品线。

In order to conduct certain assays in point-of-care blood analysis, the cell membranes of blood cells must be ruptured, a process called haemolysis. Traditionally this has been done using powerful chemical detergents, but these chemicals can intefere with the blood analysis, compromising the test. The purpose of this grant is to investigate a wholly mechanical means of haemolysis by using ultrasound-induced cavitation, a technique known as histotripsy. Histotripsy involves the application of low duty cycle, high peak pressure ultrasound pulses to a target. It has been used in a number of non-invasive therapeutic applications where it has been shown to mechanically homogenize tissue without causing heating. To our knowledge, no one has yet used histotripsy techniques for haemolysis, where it has the potential to enable high-throughput, automated blood tests without the complicating effects of chemical lysis. Histotripsy is particularly well-suited to microfluidic blood analysis since competing ultrasonic lysis techniques which use microbubbles and/or unfocused ultrasound beams are incompatible with the confined volumes and small dimensions of microfluidic systems. The project will consist of the development of a system for generating controlled, high peak pressure pulses using high intensity focused ultrasound transducers on hand in the applicants' lab. The system's ability to create cavitation will be verified through high resolution ultrasound imaging and validated through haemolysis of animal blood samples. Ultrasonic pulse amplitude, frequency and duty cycle will be optimized to enhance lysing. The project will be conducted in collaboration with Ottawa-based Alere-Epocal, a leading manufacturer of point of care microfluidic blood tests. Successful completion of the feasibility study will lead to a long term collaboration toward the incorporation of histotripsy-based lysis into the Alere-Epocal product line.