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Extended elasto-inertial microfluidics for high throughput separation in low aspect ratio spiral microchannels
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. (NANOBIOTECHNOLOGY-CLINICAL MICROFLUIDICS)ORCID iD: 0000-0001-5199-0663
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
(English)Manuscript (preprint) (Other (popular science, discussion, etc.))
Abstract [en]

Particle manipulation in viscoelastic fluid has received substantial interest because this phenomenon provides high-quality focusing. In this work, we report elasto-inertial particle focusing in spiral channels at one to two orders of magnitude higher Reynolds numbers than previously reported. We systematically investigate the interaction between inertial forces, viscoelastic forces using PEO as an elasticity enhancer and the Dean drag forces in microchannels, and report single stream particle focusing at Re > 100. Using a novel integrated 2-spiral microdevice, we applied the method to continuous focus and separate particles and report differential migration and separation 15μm from 10 μm particles at flow rate of 1 ml/min. A separation efficiency of 99% for the 15 μm and 91% for the 10μm particles was achieved. 

Keyword [en]
Inertial microfluidics, extended-elasto inertial microfluidics, circulating tumor cells, particle separation
National Category
Medical Engineering
Research subject
Biological Physics
Identifiers
URN: urn:nbn:se:kth:diva-203887OAI: oai:DiVA.org:kth-203887DiVA: diva2:1082892
Funder
Swedish Childhood Cancer Foundation
Note

QC 20170320

Available from: 2017-03-20 Created: 2017-03-20 Last updated: 2017-03-21Bibliographically approved
In thesis
1. Microfluidic based isolation of circulating tumor cells from whole blood for cancer diagnostics
Open this publication in new window or tab >>Microfluidic based isolation of circulating tumor cells from whole blood for cancer diagnostics
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Detection of circulating tumor cells (CTC) in peripheral blood is indicative of early recognition of tumor progression and such an important biomarker for early diagnosis, staging, monitoring and prognosis of cancer. However, CTC are found in very low concentrations and reliable isolation of these rare cells is challenging. Microfluidics enables precise manipulation of fluids and cells and is ideal for cell sorting methods for clinical diagnostics. The thesis contributes towards the development of microfluidic based CTC isolation methods from peripheral blood. The methods are based on size and immunoaffinity. The first part of the thesis describes the phenomenon of inertial focusing for size based cell separation at high throughputs. In paper 1, we demonstrate continuous filtration of leukocytes from diluted blood, with an efficiency of 78% at a flow rate of 2.2ml/min. In the paper 2, separation of total and subpopulation of leukocytes with a purity of 86% for granulocytes and 91% for lymphocytes is demonstrated. Furthermore, cancer cells spiked into whole blood could be separated at a yield of 88%. Finally, in paper 3 and 4 we unravel parts of the unexplored elasto-inertial microfluidics and was utilized to precisely focus the cells, as part of an integrated optofluidic micro flow cytometer device, capable to simultaneously measure fluorescence and scattering of cells and particles at a rate of 2500 particles/sec (paper 4). Second part of the thesis focuses on acoustophoresis. In (paper 5), a multifunctional acoustic microdevice was developed for isolation of cancer cells from red blood cells with a separation efficiency of 92.4% and trapping efficiency of 93%. In (paper 6), microbubbles activated acoustic cell sorter was developed for affinity based cell separation. As a proof of principle, cancer cells in a suspension were separated at an efficiency of 75%. In the third part, using cellulose nano fibrils (paper 7), we demonstrate efficiently capture and release of cancer cells at a release efficiency of 95%. Finally, a novel, single step self-assembly of spider silk proteins is introduced inside microfluidic channels for effective capture of cancer cells with 85% capture efficiency and subsequent release of captured cells with 95% release efficiency (paper 8). The novel recombinant silk modified microfluidic device was validated using pancreatic cancer patients. In summary, we have developed different microfluidic based isolation technologies for the capture and characterization of CTC.

Place, publisher, year, edition, pages
stockholm: KTH Royal Institute of Technology, 2017. 109 p.
Series
TRITA-BIO-Report, ISSN 1654-2312 ; 2017:7
National Category
Medical Engineering Medical Biotechnology
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-203889 (URN)978-91-7729-311-8 (ISBN)
Public defence
2017-04-13, Gardaulan, Folkhälsomyndigheten, Nobels väg 18, Solna, Stockholm, 10:00 (English)
Opponent
Supervisors
Funder
EU, FP7, Seventh Framework ProgrammeSwedish Childhood Cancer FoundationSwedish Research Council
Note

QC 20170321

Available from: 2017-03-20 Created: 2017-03-20 Last updated: 2017-03-23Bibliographically approved

Open Access in DiVA

The full text will be freely available from 2018-03-14 07:03
Available from 2018-03-14 07:03

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