Rare-cell enrichment by a rapid, label-free, ultrasonic isopycnic technique for medical diagnostics

Abstract

One significant challenge in medical diagnostics lies in the development of label-free methods to separate different cells within complex biological samples. Here we demonstrate a generic, low-power ultrasonic separation technique, able to enrich different cell types based upon their physical properties. For malaria, we differentiate between infected and non-infected red blood cells in a fingerprick-sized drop of blood. We are able to achieve an enrichment of circulating cells infected by the ring stage of the parasite over nonparasitized red blood cells by between two and three orders of magnitude in less than 3 seconds (enabling detection at parasitemia levels as low as 0.0005%). In a second example, we also show that our methods can be used to enrich different cell types, concentrating Trypanosoma in blood at very low levels of infection, on disposable, low-cost chips. Subtle differences in the physical properties of specific cell types are exploited in a new low-cost ultrasonic system to enrich specific cell populations (see picture; SAW=surface acoustic wave). To demonstrate the efficiency and simplicity of this method, the causative agents of malaria and sleeping sickness in blood were enriched. In this way the infection can be detected at low levels not suitable for conventional diagnostic methods. © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.