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Microfluidic Compartmentalization for Smart Materials, Medical Diagnostics and Cell Therapy
KTH, Skolan för elektroteknik och datavetenskap (EECS), Intelligenta system, Mikro- och nanosystemteknik.ORCID-id: 0000-0002-1559-3692
2022 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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. 

sted, utgiver, år, opplag, sider
Kungliga Tekniska högskolan, 2022. , s. 65
Serie
TRITA-EECS-AVL ; 2022:2
Emneord [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.
Emneord [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.
HSV kategori
Identifikatorer
URN: urn:nbn:se:kth:diva-307246ISBN: 978-91-8040-105-0 (tryckt)OAI: oai:DiVA.org:kth-307246DiVA, id: diva2:1629902
Disputas
2022-02-11, M2, Brinellvägen 64, Stockholm, 13:00 (engelsk)
Opponent
Veileder
Merknad

QC 20220120

Tilgjengelig fra: 2022-01-20 Laget: 2022-01-19 Sist oppdatert: 2025-02-17bibliografisk kontrollert
Delarbeid
1. Fluid interfacial energy drives the emergence of three-dimensional periodic structures in micropillar scaffolds
Åpne denne publikasjonen i ny fane eller vindu >>Fluid interfacial energy drives the emergence of three-dimensional periodic structures in micropillar scaffolds
Vise andre…
2021 (engelsk)Inngår i: Nature Physics, ISSN 1745-2473, E-ISSN 1745-2481, Vol. 17, nr 7, s. 794-800Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Springer Nature, 2021
HSV kategori
Identifikatorer
urn:nbn:se:kth:diva-296638 (URN)10.1038/s41567-021-01204-4 (DOI)000631498200002 ()2-s2.0-85103112237 (Scopus ID)
Merknad

QC 20220329

Tilgjengelig fra: 2021-06-10 Laget: 2021-06-10 Sist oppdatert: 2025-02-09bibliografisk kontrollert
2. Tuneable Microparticle Filters
Åpne denne publikasjonen i ny fane eller vindu >>Tuneable Microparticle Filters
Vise andre…
2019 (engelsk)Inngår i: 2019 IEEE 32nd International Conference on Micro Electro Mechanical Systems (MEMS), IEEE, 2019, s. 290-291, artikkel-id 8870801Konferansepaper, Publicerat paper (Fagfellevurdert)
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).

sted, utgiver, år, opplag, sider
IEEE, 2019
Serie
Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS), ISSN 1084-6999
HSV kategori
Identifikatorer
urn:nbn:se:kth:diva-268310 (URN)10.1109/MEMSYS.2019.8870801 (DOI)000541142100082 ()2-s2.0-85074356445 (Scopus ID)
Konferanse
32nd IEEE International Conference on Micro Electro Mechanical Systems, MEMS 2019; Seoul; South Korea; 27 January 2019 through 31 January 2019
Merknad

QC 20200310

Tilgjengelig fra: 2020-03-10 Laget: 2020-03-10 Sist oppdatert: 2024-03-15bibliografisk kontrollert
3. Digital dipstick: miniaturized bacteria detection and digital quantification for the point-of-care
Åpne denne publikasjonen i ny fane eller vindu >>Digital dipstick: miniaturized bacteria detection and digital quantification for the point-of-care
Vise andre…
2020 (engelsk)Inngår i: Lab on a Chip, ISSN 1473-0197, Vol. 20, nr 23, s. 4349-4356Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Royal Society of Chemistry (RSC), 2020
HSV kategori
Identifikatorer
urn:nbn:se:kth:diva-285877 (URN)10.1039/d0lc00793e (DOI)000592314900002 ()33169747 (PubMedID)2-s2.0-85096886096 (Scopus ID)
Merknad

QC 20201216

Tilgjengelig fra: 2020-11-11 Laget: 2020-11-11 Sist oppdatert: 2025-02-09bibliografisk kontrollert
4. A Digital Dipstick for Multiplexed Bacteria Detection
Åpne denne publikasjonen i ny fane eller vindu >>A Digital Dipstick for Multiplexed Bacteria Detection
2021 (engelsk)Inngår i: 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, s. 805-806Konferansepaper, Publicerat paper (Fagfellevurdert)
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. 

Emneord
Digital Dipstick, bioassay, bacteria, detection, urinary tract infection, Escherichia coli
HSV kategori
Identifikatorer
urn:nbn:se:kth:diva-304521 (URN)2-s2.0-85136940594 (Scopus ID)
Konferanse
The 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS 2021), 10-14 October 2021, Palm Springs, USA, and hybrid online
Prosjekter
New Diagnostics for Infectious Diseases (ND4ID)
Merknad

QC 20220302

Tilgjengelig fra: 2021-11-05 Laget: 2021-11-05 Sist oppdatert: 2023-05-15bibliografisk kontrollert
5. Slip-X-Chip: A sliding microfluidic platform with cross-flow
Åpne denne publikasjonen i ny fane eller vindu >>Slip-X-Chip: A sliding microfluidic platform with cross-flow
2022 (engelsk)Inngår i: 2022 IEEE 35th International Conference on Micro Electro Mechanical Systems Conference (MEMS), Institute of Electrical and Electronics Engineers (IEEE) , 2022, s. 912-914Konferansepaper, Poster (with or without abstract) (Fagfellevurdert)
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. 

sted, utgiver, år, opplag, sider
Institute of Electrical and Electronics Engineers (IEEE), 2022
HSV kategori
Identifikatorer
urn:nbn:se:kth:diva-307245 (URN)10.1109/MEMS51670.2022.9699532 (DOI)000784358100232 ()2-s2.0-85126394675 (Scopus ID)
Konferanse
2022 IEEE 35th International Conference on Micro Electro Mechanical Systems (MEMS)
Merknad

QC 20220524

Tilgjengelig fra: 2022-01-19 Laget: 2022-01-19 Sist oppdatert: 2022-06-25bibliografisk kontrollert
6. Cell encapsulation in alginate filaments with spider silk coating for targeted drug delivery
Åpne denne publikasjonen i ny fane eller vindu >>Cell encapsulation in alginate filaments with spider silk coating for targeted drug delivery
Vise andre…
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
HSV kategori
Identifikatorer
urn:nbn:se:kth:diva-307242 (URN)
Merknad

QC 20221102

Tilgjengelig fra: 2022-01-18 Laget: 2022-01-18 Sist oppdatert: 2022-11-02bibliografisk kontrollert
7. Rotation-induced ferromagnetism
Åpne denne publikasjonen i ny fane eller vindu >>Rotation-induced ferromagnetism
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
HSV kategori
Identifikatorer
urn:nbn:se:kth:diva-307243 (URN)
Merknad

QC 20220119

Tilgjengelig fra: 2022-01-18 Laget: 2022-01-18 Sist oppdatert: 2022-06-25bibliografisk kontrollert

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