title: Label-free microfluidic enrichment of ring-stage Plasmodium falciparum-infected red blood cells using non-inertial hydrodynamic lift.
abstract: BACKGROUND
  Understanding of malaria pathogenesis caused by Plasmodium falciparum has been greatly deepened since the introduction of in vitro culture system, but the lack of a method to enrich ring-stage parasites remains a technical challenge. Here, a novel way to enrich red blood cells containing parasites in the early ring stage is described and demonstrated.
  
  
  METHODS
  A simple, straight polydimethylsiloxane microchannel connected to two syringe pumps for sample injection and two height reservoirs for sample collection is used to enrich red blood cells containing parasites in the early ring stage (8-10 h p.i.). The separation is based on the non-inertial hydrodynamic lift effect, a repulsive cell-wall interaction that enables continuous and label-free separation with deformability as intrinsic marker.
  
  
  RESULTS
  The possibility to enrich red blood cells containing P. falciparum parasites at ring stage with a throughput of ~12,000 cells per hour and an average enrichment factor of 4.3 ± 0.5 is demonstrated.
  
  
  CONCLUSIONS
  The method allows for the enrichment of red blood cells early after the invasion by P. falciparum parasites continuously and without any need to label the cells. The approach promises new possibilities to increase the sensitivity of downstream analyses like genomic- or diagnostic tests. The device can be produced as a cheap, disposable chip with mass production technologies and works without expensive peripheral equipment. This makes the approach interesting for the development of new devices for field use in resource poor settings and environments, e.g. with the aim to increase the sensitivity of microscope malaria diagnosis.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Geislinger
authors.forename: Sherwin
authors.initials: S
authors.lastname: Chan
authors.forename: Kirsten
authors.initials: K
authors.lastname: Moll
authors.forename: Achim
authors.initials: A
authors.lastname: Wixforth
authors.forename: Mats
authors.initials: M
authors.lastname: Wahlgren
authors.affiliation: Experimental Physics I, University of Augsburg, 86159 Augsburg, Germany. thomas.franke@glasgow.ac.uk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Franke
mesh_terms: D004912:Erythrocytes / Q000469:parasitology*; D005434:Flow Cytometry / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood* / Q000469:parasitology*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D018512:Parasitemia / Q000097:blood / Q000469:parasitology; D010963:Plasmodium falciparum / Q000302:isolation & purification*