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Microfluidic Compartmentalization for Smart Materials, Medical Diagnostics and Cell Therapy
KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.ORCID iD: 0000-0002-1559-3692
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The organisation of fluids in small compartments is ubiquitous in nature, such as in the cellular composition of all life. This work explores several engineering avenues where microscale fluid compartmentalization can bring novel material properties or novel functionality in life sciences or medicine. 

Here, we introduce four unique compartmentalization methods: 1) 3D fluid self-organisation in microscaffolds (FLUID3EAMS), 2) 2D microcapillary arrays on a dipstick (Digital Dipstick), 3) a sliding microfluidic platform with cross-flow (Slip-X-Chip), and 4) compartmentalization by cutting of soft solid matter (Solidify & Cut). These methods were used in a wide range of applications. 

Within the area of smart materials, we applied FLUID3EAMS to synthesize materials with temperature-tuneable permeability and surface energy and to establish, in a well-controlled fashion, tissue-like materials in the form of 3D droplet interface bilayer networks. Solidify & Cut was used to form soft composites with a new type of magnetic behaviour, rotation-induced ferromagnetism, that allows easy reprogramming of the magnetization of magnetopolymers. 

Within the area of medical diagnostics, we applied Digital Dipstick to perform rapid digital bacterial culture in a dipstick format and obtained clinically relevant diagnostic results on samples from patients with a urinary tract infection. Furthermore, Slip-X-Chip enables particle concentration and washing as new functions in sliding microfluidic platforms, which significantly expands their potential application area. 

Finally, within the area of cell therapy, we explored the microencapsulation of high concentrations of therapeutic cells and presented a novel technique to fabricate core-shell microcapsules by exploiting the superior material properties of spider silk membranes. 

Abstract [sv]

Organisering av vätskor i små fack är allmänt förekommande i nature, t.ex. i den cellulära sammansättningen av allt liv. Det här arbetet utforskar ett flertal ingenjörsmässiga tillvägagångssätt där organisering av vätska på mikroskala kan frambringa nya egenskaper hos material eller uppnå ny funktionalitet i life science eller medicin.

Här introduceras fyra unika sätt att dela upp vätskor: 1) 3-Dimensionell självorganisation av vätskor i mikrostrukturer (FLUID3EAMS), 2) Mikrokapillära 2D-matriser på en mätsticka (Digital Dipstick), 3) en glidande mikrofluidisk platform med tvärflöde (Slip-X-Chip), och 4) uppdelning genom skärande av mjuk solid material (Solidify & Cut). De här metoderna användes i flertalet applikationsområden. 

Inom området smarta material applicerade vi FLUID3EAMS för att syntetisera material med permeabilitet och ytenergi som kunde styras med temperatur och för att etablera, i välkontrollerade former, vävnadslika material i form av ett nätverk av 3-Dimensionella dubbellager av droppgränssnitt. 

Inom området medicinsk diagnostic, applicerade vi Digital Dipstick för att utföra snabb, digital odling av bakteriekulturer i ett mätstickeformat och uppnådde kliniskt relevanta diagnostiska resultat från patienter med urinvägsinfektion. En vidareutveckling av detta koncept, Slip-X-Chip, möjliggör partikelkoncentration och sköljning som tillagda funktioner i glidande mikrofluidiska plattformar, vilket väsentligt utökar deras potentiella användningsområden. 

 Slutligen, inom området cellterapi, utforskade vi mikro-inkapsling av höga koncentrationer av terapeutiska celler och presenterade en ny teknik att framställa core-shell mikrokapslar genom att utnyttja de överlägsna materialegenskaperna hos silkesmembran från spindlar. 

Place, publisher, year, edition, pages
Kungliga Tekniska högskolan, 2022. , p. 65
Series
TRITA-EECS-AVL ; 2022:2
Keywords [en]
Microfluidics, microfabrication, compartmentalization, partitioning, droplet microfluidics, self-assembly, 3D microarrays, soft composites, beads, particles, core-shell particle, point-of-care, diagnostics, dipstick, digital bioassays, lab-on-a-chip, urinary tract infection, bacteria detection, E. coli, cell encapsulation, hydrogel, cell therapy, spider silk, magnetic metamaterials.
Keywords [sv]
Mikrofluidik, mikrotillverkning, kompartmentalisering, partitionering, droppmikrofluidik, självmontering, 3D-mikromatriser, mjuka kompositer, pärlor, partiklar, kärna-skalpartikel, vårdpunkt, diagnostik, mätsticka, digitala bioanalyser, laboration-a-chip, urinvägsinfektion, bakteriedetektering, E. coli, cellinkapsling, hydrogel, cellterapi, spindelsilke, magnetiska metamaterial.
National Category
Engineering and Technology Biomaterials Science Biomedical Laboratory Science/Technology Composite Science and Engineering Other Electrical Engineering, Electronic Engineering, Information Engineering Medical Biotechnology Nano Technology
Identifiers
URN: urn:nbn:se:kth:diva-307246ISBN: 978-91-8040-105-0 (print)OAI: oai:DiVA.org:kth-307246DiVA, id: diva2:1629902
Public defence
2022-02-11, M2, Brinellvägen 64, Stockholm, 13:00 (English)
Opponent
Supervisors
Note

QC 20220120

Available from: 2022-01-20 Created: 2022-01-19 Last updated: 2022-09-19Bibliographically approved
List of papers
1. Fluid interfacial energy drives the emergence of three-dimensional periodic structures in micropillar scaffolds
Open this publication in new window or tab >>Fluid interfacial energy drives the emergence of three-dimensional periodic structures in micropillar scaffolds
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2021 (English)In: Nature Physics, ISSN 1745-2473, E-ISSN 1745-2481, Vol. 17, no 7, p. 794-800Article in journal (Refereed) Published
Abstract [en]

Structures that are periodic on a microscale in three dimensions are abundant in nature, for example, in the cellular arrays that make up living tissue. Such structures can also be engineered, appearing in smart materials(1-4), photonic crystals(5), chemical reactors(6), and medical(7) and biomimetic(8) technologies. Here we report that fluid-fluid interfacial energy drives three-dimensional (3D) structure emergence in a micropillar scaffold. This finding offers a rapid and scalable way of transforming a simple pillar scaffold into an intricate 3D structure that is periodic on a microscale, comprising a solid microscaffold, a dispersed fluid and a continuous fluid. Structures generated with this technique exhibit a set of unique features, including a stationary internal liquid-liquid interface. Using this approach, we create structures with an internal liquid surface in a regime of interest for liquid-liquid catalysis. We also synthesize soft composites in solid, liquid and gas combinations that have previously not been shown, including actuator materials with temperature-tunable microscale pores. We further demonstrate the potential of this method for constructing 3D materials that mimic tissue with an unprecedented level of control, and for microencapsulating human cells at densities that address an unresolved challenge in cell therapy.

Place, publisher, year, edition, pages
Springer Nature, 2021
National Category
Fluid Mechanics and Acoustics
Identifiers
urn:nbn:se:kth:diva-296638 (URN)10.1038/s41567-021-01204-4 (DOI)000631498200002 ()2-s2.0-85103112237 (Scopus ID)
Note

QC 20220329

Available from: 2021-06-10 Created: 2021-06-10 Last updated: 2024-01-18Bibliographically approved
2. Tuneable Microparticle Filters
Open this publication in new window or tab >>Tuneable Microparticle Filters
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2019 (English)In: 2019 IEEE 32nd International Conference on Micro Electro Mechanical Systems (MEMS), IEEE, 2019, p. 290-291, article id 8870801Conference paper, Published paper (Refereed)
Abstract [en]

We introduce microparticle filters with temperature tuneable size cut-off and surface energy. At room temperature, the filter cut-off is 164 ±23 μm, and the filter is water-absorbing/oil-repelling (hydrophilic). At 50 °C, the filter cut-off is 695±31 μm, and the filter is oil-absorbing/water-repelling (hydrophobic).

Place, publisher, year, edition, pages
IEEE, 2019
Series
Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS), ISSN 1084-6999
National Category
Nano Technology
Identifiers
urn:nbn:se:kth:diva-268310 (URN)10.1109/MEMSYS.2019.8870801 (DOI)000541142100082 ()2-s2.0-85074356445 (Scopus ID)
Conference
32nd IEEE International Conference on Micro Electro Mechanical Systems, MEMS 2019; Seoul; South Korea; 27 January 2019 through 31 January 2019
Note

QC 20200310

Available from: 2020-03-10 Created: 2020-03-10 Last updated: 2024-03-15Bibliographically approved
3. Digital dipstick: miniaturized bacteria detection and digital quantification for the point-of-care
Open this publication in new window or tab >>Digital dipstick: miniaturized bacteria detection and digital quantification for the point-of-care
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2020 (English)In: Lab on a Chip, ISSN 1473-0197, Vol. 20, no 23, p. 4349-4356Article in journal (Refereed) Published
Abstract [en]

Established digital bioassay formats, digital PCR and digital ELISA, show extreme limits of detection, absolute quantification and high multiplexing capabilities. However, they often require complex instrumentation, and extensive off-chip sample preparation. In this study, we present a dipstick-format digital biosensor (digital dipstick) that detects bacteria directly from the sample liquid with a minimal number of steps: dip, culture, and count. We demonstrate the quantitative detection of Escherichia coli (E. coli) in urine in the clinically relevant range of 102 –105 CFU ml−1 for urinary tract infections. Our format shows 89% sensitivity to detect E. coli in clinical urine samples (n = 28) when it is compared to plate culturing (gold standard). The significance and uniqueness of this diagnostic test format is that it allows a non-trained operator to detect urinary tract infections in the clinically relevant range in the home setting.

Place, publisher, year, edition, pages
Royal Society of Chemistry (RSC), 2020
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:kth:diva-285877 (URN)10.1039/d0lc00793e (DOI)000592314900002 ()33169747 (PubMedID)2-s2.0-85096886096 (Scopus ID)
Note

QC 20201216

Available from: 2020-11-11 Created: 2020-11-11 Last updated: 2022-07-11Bibliographically approved
4. A Digital Dipstick for Multiplexed Bacteria Detection
Open this publication in new window or tab >>A Digital Dipstick for Multiplexed Bacteria Detection
2021 (English)In: The 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS 2021), 10-14 October 2021, Palm Springs, USA, and hybrid online, 2021, p. 805-806Conference paper, Published paper (Refereed)
Abstract [en]

In this study, we demonstrate a digital bacterial detection assay in a dipstick format that can identify and quantitate Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis, i.e., three of the most common (>90%) bacteria causing urinary tract infections (UTIs). The operation involves nothing more than dipping the stick in urine for a few seconds and let the stick incubate for 10-12 h before read-out. Each of the 180 miniaturised culture wells in the stick contain chromogenic agar and change colour if they contain a CFU. The colour of the wells identifies the presence of a specific type of bacteria; the number of coloured wells indicates the concentration. This format allows detection and quantification at a potentially low cost and without the need for complicated external equipment or technical skills. 

Keywords
Digital Dipstick, bioassay, bacteria, detection, urinary tract infection, Escherichia coli
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:kth:diva-304521 (URN)2-s2.0-85136940594 (Scopus ID)
Conference
The 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS 2021), 10-14 October 2021, Palm Springs, USA, and hybrid online
Projects
New Diagnostics for Infectious Diseases (ND4ID)
Note

QC 20220302

Available from: 2021-11-05 Created: 2021-11-05 Last updated: 2023-05-15Bibliographically approved
5. Slip-X-Chip: A sliding microfluidic platform with cross-flow
Open this publication in new window or tab >>Slip-X-Chip: A sliding microfluidic platform with cross-flow
2022 (English)In: 2022 IEEE 35th International Conference on Micro Electro Mechanical Systems Conference (MEMS), Institute of Electrical and Electronics Engineers (IEEE) , 2022, p. 912-914Conference paper, Poster (with or without abstract) (Refereed)
Abstract [en]

In sliding microfluidic platforms (“SlipChip” [1]), two plates with microfluidic wells slide in close contact to perform multiplexed reactions in a single operation. In- plane “sliding-flow” liquid transport, however, limits the potential assay operations to 1) sample compartmentalization/metering, 2) reagent addition, 3) mixing, and 4) aliquoting. Here, we introduce a three-plate sliding microfluidics platform, “Slip-X-Chip”, that additionally includes out-of-plane “cross-flow” liquid transport. Slip-X-Chip allows two additional assay operations: 5) sample concentration and 6) liquid exchange/washing, while retaining the simplicity of operation (one-step operation; no precise pipetting required; no external equipment). These additional assay operations extend the range and complexity of applications enabled by sliding microfluidics. We here demonstrate 1) splitting bead solutions in compartments with different concentrations and 2) compartmentalizing human cells from solution, followed by a viability assay. We foresee that Slip-X-Chip could be further adapted to, e.g., cell counting, cell staining, or ELISA. 

Place, publisher, year, edition, pages
Institute of Electrical and Electronics Engineers (IEEE), 2022
National Category
Nano Technology
Identifiers
urn:nbn:se:kth:diva-307245 (URN)10.1109/MEMS51670.2022.9699532 (DOI)000784358100232 ()2-s2.0-85126394675 (Scopus ID)
Conference
2022 IEEE 35th International Conference on Micro Electro Mechanical Systems (MEMS)
Note

QC 20220524

Available from: 2022-01-19 Created: 2022-01-19 Last updated: 2022-06-25Bibliographically approved
6. Cell encapsulation in alginate filaments with spider silk coating for targeted drug delivery
Open this publication in new window or tab >>Cell encapsulation in alginate filaments with spider silk coating for targeted drug delivery
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(English)Manuscript (preprint) (Other academic)
National Category
Biomaterials Science
Identifiers
urn:nbn:se:kth:diva-307242 (URN)
Note

QC 20221102

Available from: 2022-01-18 Created: 2022-01-18 Last updated: 2022-11-02Bibliographically approved
7. Rotation-induced ferromagnetism
Open this publication in new window or tab >>Rotation-induced ferromagnetism
(English)Manuscript (preprint) (Other academic)
National Category
Condensed Matter Physics Composite Science and Engineering
Identifiers
urn:nbn:se:kth:diva-307243 (URN)
Note

QC 20220119

Available from: 2022-01-18 Created: 2022-01-18 Last updated: 2022-06-25Bibliographically approved

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