A Novel Sample Preparation Concept for Sepsis Diagnostics Using High Frequency Electric Fields

Abstract

Despite their high potential to replace the time consuming gold standard blood culture for infection diagnosis from whole blood, molecular biology based techniques often lack sensitivity and specificity due to the high human background in complex biological samples such as blood. Concerning the realization of a point-of-care device for sepsis diagnosis which would enable immediate targeted antimicrobial therapy, new, implementable and scalable sample preparation strategies are urgently needed that aim at reducing the human background. In this paper we report a first proof-of-principle for such a novel concept of selective human blood cell depletion preserving bacterial pathogen integrity by using high frequency electric fields. By thin film electrical passivation of the electrode material, ohmic current through the biological sample, which causes unspecific cell lysis, is drastically reduced. With the developed SiO2-passivated electrical cell lysis unit (ECLU), cell specific lysis of up to 75.3 % of the total human blood cells could be shown with less than 10 % loss of E. Coli viability. Additionally, a small electrode distance of 25 μm reduced the required voltage for selective cell lysis to a range of 8-20 V. The results presented here show great potential for the further development of fully automated and integrated cell selective sample preparation.