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All silica fibre microflow cytometer
KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.ORCID iD: 0000-0001-5199-0663
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Flow cytometry is currently the gold standard for analysis of cells in the medical laboratory and biomedical research. Fuelled by the need of point-of-care diagnosis, a significant effort has been made to miniaturize and reduce cost of flow cytometers. However, despite recent advances, current microsystems remain less versatile and much slower than their large-scale counterparts. In this work, an all-silica fibre microflow cytometer is presented that measures fluorescence and scattering from particles and cells. It integrates cell transport in circular capillaries and light delivery by optical fibres   Single-stream cell focusing is performed by Elasto-inertial microfluidics to guarantee optical accuracy and sensitivity.  The capability of this technique is extended to high flow rates (up to 800 µl/min), enabling throughput of 2500 particles/s. The robust, portable and low-cost system described here could be the basis for a point-of-care flow cytometer with a performance comparable to commercial systems. 

Keyword [en]
Flow cytometry, fiber optics
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:kth:diva-203953OAI: oai:DiVA.org:kth-203953DiVA: diva2:1083230
Note

QC 20170321

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 2018-03-23 15:43
Available from 2018-03-23 15:43

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