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

为了在即时血液分析中进行某些检测，必须对血细胞的细胞膜进行检测

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.