Abstract
Rapidly isolating rare targets from larger, clinically relevant fluid volumes remains an unresolved problem in biomedicine and diagnosis. Here, we describe how 3D particle sorting can enrich targets at ultralow concentrations over 100-fold within minutes not possible with conventional approaches. Current clinical devices based on biochemical extraction and microfluidic solutions typically require high concentrations and/or can only process sub-milliliter volumes in time. In a proof-of-concept application, we isolated bacteria from whole blood as demanded for rapid sepsis diagnosis where minimal numbers of bacteria need to be found in a 1–10 mL blood sample. After sample encapsulation in droplets and target enrichment with the 3D particle sorter within a few minutes, downstream analyses were able to identify bacteria and test for antibiotic susceptibility, information which is critical for successful treatment of bloodstream infections.
Highlights
Isolating rare targets from larger, clinically relevant fluid volumes remains an unresolved problem in biomedicine and diagnosis
Blood culture enrichment can take 24–72 h followed by bacterial identification (ID) and antibiotic susceptibility testing (AST), typically within an additional 4–24 h
Particle enrichment in a microfluidic device is limited by fluid friction typically restricting sample flow rates to ~ 5 μL/min, not practical for many diagnostic applications that require multi-mL samples including B SIs17
Summary
Isolating rare targets from larger, clinically relevant fluid volumes remains an unresolved problem in biomedicine and diagnosis. In a clinical setting with many possible unknown targets, the large number of repeated specific tests required to achieve high test sensitivity is often not compatible with limited sample amounts and a demanding time-to-result. Several studies have demonstrated that reduced time-to-result for bacterial ID/AST using rapid tests is directly correlated with reduced mortality rates and healthcare costs[27,28,29,30,31] To address this issue, our workflow demonstration comprises upstream droplet encapsulation of the raw sample (Fig. 1a), detection and isolation of bacteria positive droplets within minutes by 3D particle sorting (Fig. 1b), and downstream sequencing and AST (Fig. 1c). Screening for targets such as antibody-producing B cells should be feasible within a single working day of ~ 8 h, a major bottleneck that our 3D particle sorting approach is able to overcome
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