A more effective treatment of bacteremia requires a diagnostic platform that is both sensitive, accurate and rapid. Currently, clinical laboratory techniques require growth of bacteria prior to diagnosis, take days to complete, and leave empiric therapy and broad spectrum antibiotics as the only option at the onset of treatment. In order to bypass this growth requirement, we engineered a system that purifies bacteria from blood to improve performance in a bacteriophage-based luminescence assay. To perform the purification, we used acoustophoresis in plastic microfluidic chips, enabling future development into a low cost point-of-care system. Acoustophoresis achieves differential separation on the basis of size differences between bacteria and blood cells. We show isolation of three known pathogen species, including members of both Gram-negative and positive-bacteria from blood, and show isolation at clinically relevant concentrations. Using the device as a preparation step prior to the bacteriophage-based luminescence assay, we demonstrate a 33-fold improvement in limit of detection, compared with the unpurified sample, achieving a limit of detection of 6 bacteria.
Acoustic manipulation has emerged as a versatile method for microfluidic separation and concentration of particles and cells. Most recent demonstrations of the technology use piezoelectric actuators to excite resonant modes in silicon or glass microchannels. Here, we focus on acoustic manipulation in disposable, plastic microchannels in order to enable a low-cost processing tool for point-of-care diagnostics. Unfortunately, the performance of resonant acoustofluidic devices in plastic is hampered by a lack of a predictive model. In this paper, we build and test a plastic blood-bacteria separation device informed by a design of experiments approach, parametric rapid prototyping, and screening by image-processing. We demonstrate that the new device geometry can separate bacteria from blood while operating at 275% greater flow rate as well as reduce the power requirement by 82%, while maintaining equivalent separation performance and resolution when compared to the previously published plastic acoustofluidic separation device.
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