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Elasto-inertial microfluidics for bacteria separation from whole blood for sepsis diagnostics
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. mafaridi@kth.se. (Clinical Microfluidics)ORCID iD: 0000-0003-1176-0905
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. (Clinical Microfluidics)ORCID iD: 0000-0001-5199-0663
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. (Clinical Microfluidics)
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
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2017 (English)In: Journal of Nanobiotechnology, ISSN 1477-3155, E-ISSN 1477-3155, Vol. 15, article id 3Article in journal (Refereed) Published
Abstract [en]

Background: Bloodstream infections (BSI) remain a major challenge with high mortality rate, with an incidence that is increasing worldwide. Early treatment with appropriate therapy can reduce BSI-related morbidity and mortality. However, despite recent progress in molecular based assays, complex sample preparation steps have become critical roadblock for a greater expansion of molecular assays. Here, we report a size based, label-free, bacteria separation from whole blood using elasto-inertial microfluidics.

Results: In elasto-inertial microfluidics, the viscoelastic flow enables size based migration of blood cells into a non- Newtonian solution, while smaller bacteria remain in the streamline of the blood sample entrance and can be sepa- rated. We first optimized the flow conditions using particles, and show continuous separation of 5 μm particles from 2 μm at a yield of 95% for 5 μm particle and 93% for 2 μm particles at respective outlets. Next, bacteria were continu- ously separated at an efficiency of 76% from undiluted whole blood sample.

Conclusion: We demonstrate separation of bacteria from undiluted while blood using elasto-inertial microfluidics. The label-free, passive bacteria preparation method has a great potential for downstream phenotypic and molecular analysis of bacteria. 

Place, publisher, year, edition, pages
BioMed Central, 2017. Vol. 15, article id 3
Keywords [en]
Micro particle separation, Elasto-inertial microfluidics, Sepsis, Sample preparation
National Category
Medical Biotechnology
Identifiers
URN: urn:nbn:se:kth:diva-200300DOI: 10.1186/s12951-016-0235-4ISI: 000391073000001Scopus ID: 2-s2.0-85008198016OAI: oai:DiVA.org:kth-200300DiVA, id: diva2:1068014
Projects
RAPP_ID
Funder
EU, European Research Council, 115153
Note

QC 20170124

Available from: 2017-01-24 Created: 2017-01-24 Last updated: 2017-11-29Bibliographically approved
In thesis
1. Bioparticle Manipulation using Acoustophoresis and Inertial Microfluidics
Open this publication in new window or tab >>Bioparticle Manipulation using Acoustophoresis and Inertial Microfluidics
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Despite the many promising advances made in microfluidics, sample preparation remains the single largest challenge and bottleneck in the field of miniaturised diagnostics. This thesis is focused on the development of sample preparation methods using active and passive particle manipulation techniques for point of care diagnostic applications. The active technique is based on acoustophoresis (acoustic manipulation) while the passive method is based on inertial microfluidics (hydrodynamic manipulation). In paper I, acoustic capillary-based cavity resonator was used to study aggregation of silica and polystyrene particles. We found that silica particles show faster aggregation time (5.5 times) and larger average area of aggregates (3.4 times) in comparison to polystyrene particles under the same actuation procedure. The silica particles were then used for acoustic based bacteria up-concentration. In paper II, a microfluidic-based microbubbles activated acoustic cell sorting technique was developed for affinity based cell separation. As a proof of principle, separation of cancer cell line in a suspension with better than 75% efficiency is demonstrated. For the passive sample preparation, inertial and elasto-inertial microfluidic approach that uses geometry-induced hydrodynamic forces for continuous size-based sorting of particles in a flow-through fashion were studied and applied for blood processing (paper III-V). In paper III, a simple ushaped curved channel was used for inertial microfluidics based enrichment of white blood cells from diluted whole blood. A filtration efficiency of 78% was achieved at a flow rate of 2.2 ml/min. In paper IV, elasto-inertial microfluidics where viscoelastic flow enables size-based migration of cells into a non- Newtonian solution, was used to continuously separate bacteria from unprocessed whole blood for sepsis diagnostics. Bacteria were continuously separated at an efficiency of 76% from undiluted whole blood sample. Finally, in paper V, the inertial and elasto-inertial techniques were combined with a detection platform to demonstrate an integrated miniaturized flow cytometer. The all-optical-fiber technology based system allows for simultaneous measurements of fluorescent and scattering data at 2500 particles/s. The use of inertial and acoustic techniques for sample preparation and development of an integrated detection platform may allow for further development and realization of point of care testing (POCT) systems.

Place, publisher, year, edition, pages
Stockholm, Sweden: Kungliga Tekniska högskolan, 2017. p. 68
Series
TRITA-BIO-Report, ISSN 1654-2312 ; 2017:4
National Category
Medical Biotechnology
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-200304 (URN)978-91-7729-264-7 (ISBN)
Public defence
2017-02-16, Gard-Aulan, Nobels vägen 18, Solna, Stockholm, 10:00 (English)
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Note

QC 20170124

Available from: 2017-01-24 Created: 2017-01-24 Last updated: 2017-01-24Bibliographically approved

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