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- Tran, Si Hoai Trung
(author)
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Deterministic Lateral Displacement for Cell Separation
- 2019
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Doctoral thesis (other academic/artistic)abstract
- In the fields of medicine and biology, the separation of particles is a central step in many preparative and analytical processes. Deterministic Lateral Displacement (DLD) has been a promising technique in the field of microfluidic particle and cell sorting, specifically for label-free separation with several applications of sorting by size, morphology, and deformation reported in the literature over the last decade.Separation of cancer cells from a heterogeneous sample is known as a challenging task due to the similarity of the cells involved. Deformability is a potential bio-marker for cell isolation where specific molecular markers are lacking. In the thesis, we demonstrate an efficient measurement tool for cell deformation in the DLD device as well as a sorting tool for cell isolation based on deformability among breast cancer cells (MCF7), human breast cells (MCF10A) and metastasizing breast cancer cells (MDA-MB-231). (Paper 2).Many sorting problems require careful optimization for a successful result. We have approached this problem in two ways: a combination of electrokinetics and DLD for controlling the rotation of RBCs (Paper 3) or through the deformation of the DLD devices by control of the driving pressure (Paper 5).An important limitation of microfluidics is that conventional pumps are difficult to transport, need trained personnel and are associated with high running costs. They are often not fully compatible with point-of-care applications, especially in resource-poor settings. The second part of this thesis therefore focuses on alternative ways to operate microfluidic DLD devices, to ensure portability and user friendliness. A combination of an open DLD device and a paper-based pump is a key component of this approach (Paper 1). Several sorting applicationsinvolving blood fractionation, trypanosome enrichment, and breast cancer cell extraction are performed efficiently in terms of potential purity and capture rate. Moreover, our open-fluidics platform is shown to have advantages with regards to easy cleaning, reusability and electrokinetic integration. Finally, an approach for fast and easy fabrication for devices based on single or multilayer stacks is discussed in Paper 4.
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| 2. |
- Tran, Si Hoai Trung, et al.
(author)
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Open channel deterministic lateral displacement for particle and cell sorting
- 2017
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In: Lab on a Chip - Miniaturisation for Chemistry and Biology. - : Royal Society of Chemistry (RSC). - 1473-0197. ; 17:21, s. 3592-3600
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Journal article (peer-reviewed)abstract
- We present the use of capillary driven flow over patterned surfaces to achieve cheap and simple, but powerful separation of biologically relevant particle systems. The wide use of microfluidics is often hampered by the propensity for devices to clog due to the small channel sizes and the inability to access the interior of devices for cleaning. Often the devices can only be used for a limited duration and most frequently only once. In addition the cost and power requirements of flow control equipment limits the wider spread of the devices. We address these issues by presenting a simple particle- and cell-sorting scheme based on controlled fluid flow on a patterned surface. The open architecture makes it highly robust and easy to use. If clogging occurs it is straightforward to rinse the device and reuse it. Instead of external mechanical pumps, paper is used as a capillary pump. The different fractions are deposited in the paper and can subsequently be handled independently by simply cutting the paper for downstream processing and analyses. The sorting, based on deterministic lateral displacement, performs equivalently well in comparison with standard covered devices. We demonstrate successful separation of cancer cells and parasites from blood with good viability and with relevance for diagnostics and sample preparation. Sorting a mixture of soil and blood, we show the potential for forensic applications.
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| 3. |
- Tran, Si Hoai Trung, et al.
(author)
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Particle separation and diffusion based limitation
- 2016
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In: 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016. - 9780979806490 ; , s. 1545-1546
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Conference paper (peer-reviewed)abstract
- Deterministic lateral displacement (DLD) is a promising method for particle separation in the micrometer range, the proof of principle of which has been demonstrated to be successful in fields such as biomedicine and physics [1]. However, the enhanced particle dispersion (Figure 1 & 2) arising when separating very small particles (such as viruses and proteins) constitutes the main functional barrier of DLD-based devices. In this study theoretical predictions made by [2, 3] have been experimentally observed, the relation of the dispersion effect with the construction parameters of the bumper arrays has been investigated, and a strategy for dispersion reduction is suggested.
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| 4. |
- Tran, Si Hoai Trung, et al.
(author)
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Sorting breast cancer cells based on deformability
- 2015
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In: MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - 9780979806483 ; , s. 364-366
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Conference paper (peer-reviewed)abstract
- Due to their direct coupling to the physiology of the cells, the physical properties are especially attractive as markers for sorting and characterization of cancer cells. Where molecular surface markers are lacking, the physical properties can instead serve as inherent markers for separation. This is especially interesting for cancer cells where there are indications that soft cells are more metastatic than hard cells. Our work is expected to provide a deeper understanding of deformability based sorting based on deterministic lateral displacement (DLD). This will subsequently be used to optimize DLD devices for characterization and fractionation of cancer cells into subpopulations of different mechanical properties. Our aim is to develop a device to help oncologists gain more accurate prognoses and better monitoring of the effect of treatment.
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| 5. |
- Tran, Si Hoai Trung, et al.
(author)
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Surface based fluidics for particle sorting
- 2015
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In: MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - 9780979806483 ; , s. 2136-2137
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Conference paper (peer-reviewed)abstract
- We have created devices that are extremely simple to fabricate, function without pumps, are reusable and capable of dealing with very large differences in particle sizes without clogging. Our new approach to microfluidic particle sorting is precise enough for applications in blood fractionation, cancer cell sorting, parasite detection and sample decomplexing in general. We achieve this using Deterministic Lateral Displacement (DLD) in an open channel where particles flow across a patterned surface under the impetus of capillary forces alone.
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