Microfluidic based isolation of circulating tumor cells from whole blood for cancer diagnostics
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
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.
TRITA-BIO-Report, ISSN 1654-2312 ; 2017:7
Medical Engineering Medical Biotechnology
Research subject Biotechnology
IdentifiersURN: urn:nbn:se:kth:diva-203889ISBN: 978-91-7729-311-8 (electronic)OAI: oai:DiVA.org:kth-203889DiVA: diva2:1083033
2017-04-13, Gardaulan, Folkhälsomyndigheten, Nobels väg 18, Solna, Stockholm, 10:00 (English)
Hjort, Klas, Professor
Russom, Aman, ASSOCIATE PROFESSOR
FunderEU, FP7, Seventh Framework ProgrammeSwedish Childhood Cancer FoundationSwedish Research Council
QC 201703212017-03-202017-03-202017-03-23Bibliographically approved
List of papers