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

In order to conduct certain assays in point-of-care blood analysis, the cell membranes of blood cells must beruptured, 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 toinvestigate a wholly mechanical means of haemolysis by using ultrasound-induced cavitation, a techniqueknown as histotripsy. Histotripsy involves the application of low duty cycle, high peak pressure ultrasoundpulses to a target. It has been used in a number of non-invasive therapeutic applications where it has beenshown to mechanically homogenize tissue without causing heating. To our knowledge, no one has yet usedhistotripsy techniques for haemolysis, where it has the potential to enable high-throughput, automated bloodtests without the complicating effects of chemical lysis. Histotripsy is particularly well-suited to microfluidicblood analysis since competing ultrasonic lysis techniques which use microbubbles and/or unfocusedultrasound 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 pulsesusing high intensity focused ultrasound transducers on hand in the applicants' lab. The system's ability tocreate cavitation will be verified through high resolution ultrasound imaging and validated through haemolysisof animal blood samples. Ultrasonic pulse amplitude, frequency and duty cycle will be optimized to enhancelysing.The project will be conducted in collaboration with Ottawa-based Alere-Epocal, a leading manufacturer ofpoint of care microfluidic blood tests. Successful completion of the feasibility study will lead to a long termcollaboration toward the incorporation of histotripsy-based lysis into the Alere-Epocal product line.