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Controlled Lateral Positioning of Microparticles Inside Droplets Using Acoustophoresis
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.ORCID iD: 0000-0003-3618-9944
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2015 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 87, no 20, 10521-10526 p.Article in journal (Refereed) Published
Abstract [en]

In this paper, we utilize bulk acoustic waves to control the position of micropartides inside droplets in two-phase microfluidic systems and demonstrate a method to enrich the micropartides. In droplet microfluidics, different unit operations are combined and integrated on-chip to miniaturize complex biochemical assays. We present a droplet unit operation capable of controlling the position of micropartides during a trident shaped droplet split. An acoustic standing wave field is generated in the microchannel, and the acoustic forces direct the encapsulated micropartides to the center of the droplets. The method is generic, requires no labeling of the micropartides, and is operated in a noncontact fashion. It was possible to achieve 2+-fold enrichment of polystyrene beads (5 mu m in diameter) in the center daughter droplet with an average recovery of 89% of the beads. Red blood cells were also successfully manipulated inside droplets. These results show the possibility to use acoustophoresis in two-phase systems to enrich micropartides and open up the possibility for new droplet-based assays that are not performed today.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2015. Vol. 87, no 20, 10521-10526 p.
Keyword [en]
Bioassay, Biochips, Microarrays, Microfluidics, Position control, Acoustic standing wave, Biochemical assay, Bulk acoustic waves, Daughter droplets, Droplet microfluidics, Micro fluidic system, Polystyrene beads, Two phase systems
National Category
Robotics Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
URN: urn:nbn:se:kth:diva-176960DOI: 10.1021/acs.analchem.5b02746ISI: 000363348300051PubMedID: 26422760ScopusID: 2-s2.0-84945288371OAI: oai:DiVA.org:kth-176960DiVA: diva2:883065
Note

QC 20151216

Available from: 2015-12-16 Created: 2015-11-13 Last updated: 2016-09-19Bibliographically approved
In thesis
1. Droplet microfluidics for single cell and nucleic acid analysis
Open this publication in new window or tab >>Droplet microfluidics for single cell and nucleic acid analysis
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Droplet microfluidics is an emerging technology for analysis of single cells and biomolecules at high throughput. The controlled encapsulation of particles along with the surrounding microenvironment in discrete droplets, which acts as miniaturized reaction vessels, allows millions of particles to be screened in parallel. By utilizing the unit operations developed to generate, manipulate and analyze droplets, this technology platform has been used to miniaturize a wide range of complex biological assays including, but not limited to, directed evolution, rare cell detection, single cell transcriptomics, rare mutation detection and drug screening.

The aim of this thesis is to develop droplet microfluidics based methods for analysis of single cells and nucleic acids. In Paper I, a method for time-series analysis of mammalian cells, using automated fluorescence microscopy and image analysis technique is presented. The cell-containing droplets were trapped on-chip and imaged continuously to assess the viability of hundreds of isolated individual cells over time. This method can be used for studying the dynamic behavior of cells. In Paper II, the influence of droplet size on cell division and viability of mammalian cell factories during cultivation in droplets is presented. The ability to achieve continuous cell division in droplets will enable development of mammalian cell factory screening assays in droplets. In Paper III, a workflow for detecting the outcome of droplet PCR assay using fluorescently color-coded beads is presented. This workflow was used to detect the presence of DNA biomarkers associated with poultry pathogens in a sample. The use of color-coded detection beads will help to improve the scalability of the detection panel, to detect multiple targets in a sample. In Paper IV, a novel unit operation for label-free enrichment of particles in droplets using acoustophoresis is presented. This technique will be useful for developing droplet-based assays that require label-free enrichment of cells/particles and removal of droplet content. In general, droplet microfluidics has proven to be a versatile tool for biological analysis. In the years to come, droplet microfluidics could potentially be used to improve clinical diagnostics and bio-based production processes.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2016. 58 p.
Series
TRITA-BIO-Report, ISSN 1654-2312 ; 2016:17
Keyword
Acoustophoresis, Biomarker detection, Cell behavior analysis, Cell factories, Droplet microfluidics, Droplet PCR, High throughput biology, Label-free enrichment, Single cell analysis
National Category
Other Engineering and Technologies not elsewhere specified
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-192668 (URN)978-91-7729-125-1 (ISBN)
Public defence
2016-10-21, Gard-aulan, Nobels väg 18, Solna, 10:00 (English)
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Supervisors
Note

QC 20160926

Available from: 2016-09-26 Created: 2016-09-19 Last updated: 2016-09-26Bibliographically approved

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