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

为了在护理点血液分析中进行某些分析，血细胞的细胞膜必须 破裂，这一过程称为溶血。传统上，这是使用强力化学洗涤剂来完成的， 但这些化学物质会干扰血液分析，影响检测。这笔赠款的目的是 利用超声诱导空化技术探索一种完全机械的溶血方法 这就是所谓的组织旅行。组织摩擦学涉及低占空比、高峰值压力超声的应用 向目标发出脉冲。它已被用于许多非侵入性治疗应用中 可以机械地使组织均质，而不会引起加热。据我们所知，还没有人用过 溶血的组织摩擦学技术，它有可能实现高通量、自动化的血液 没有化学裂解的复杂影响的测试。组织摩擦学特别适用于微流控 自使用微泡和/或无聚焦的竞争超声裂解技术以来的血液分析 超声波束与微流控系统的受限体积和小尺寸不相容。 该项目将包括开发一种产生受控、高峰值压力脉冲的系统 在申请人的实验室使用手头的高强度聚焦超声换能器。该系统的能力 将通过高分辨率超声成像和溶血验证产生空化 动物血液样本。将优化超声脉冲幅度、频率和占空比，以提高 歌唱。 该项目将与总部位于渥太华的Alere-Epocal合作进行，Alere-Epocal是一家领先的 护理点微流控血液测试。成功完成可行性研究将带来长远的结果 合作将组织摩擦学为基础的裂解物纳入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.