Acoustofluidic Blood Component Sample Preparation and Processing in Medical Applications

Recent developments of bulk acoustofluidic technology (BAW – bulk acoustic wave) in biomedical applications is described in this chapter. The basic principles for setting up an acoustic standing wave in a microchannel in 1 or 2 dimensions in the transversal direction to flow is outlined. BAW acoustofluidics is a preferred solution as compared to SAW based acoustofluidics due to the relatively higher acoustic energies that can be accomplished in BAW systems. This in turn lends BAW technology to perform cell manipulation based handling in a sufficiently high flow through format that can fulfill many biomedical and bioanalytical applications. Several unit operations for BAW based cell handling have today reached a level of maturity where these are being integral components in cytometry and cell processing instrumentation. Most of these applications are still realized at an analytical level and have not yet reached process scale or therapeutic scale throughput. However, intense developments are in progress to also reach into this domain of larger scale processing since the performance and label free operation offered from BAW systems would significantly impact current bioprocess industry and clinical practice. The importance of having full control of the buffer systems used is discussed since poorly matched buffers/fluids, with respect to the acoustic properties (acoustic impedance), may significantly impact the processing outcome as a consequence of acoustically driven fluid relocation. Also, the challenge of manipulating smaller bioparticles, e.g. bacteria, is discussed and strategies to tackle the fact that the inherent acoustic streaming in acoustic standing wave based microfluidics may be counteracting the desired alignment of cell/particles defined by the acoustic standing wave. A focus is put on applications in blood component processing, where unit operations such as cell separation (WBC, RBC, WBC subpopulations, CTC and platelets), buffer exchange and concentrating cell samples have become important modalities in cell based microfluidics. The current state of diagnostic BAW applications such as blood plasma separation, circulating tumor cell (CTC) isolation, rapid hematocrit determination and bacteria enrichment/purification in sepsis are discussed.