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Digital dipstick: miniaturized bacteria detection and digital quantification for the point-of-care
KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.ORCID iD: 0000-0002-1559-3692
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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. Vol. 20, no 23, p. 4349-4356
National Category
Medical Laboratory Technologies
Identifiers
URN: urn:nbn:se:kth:diva-285877DOI: 10.1039/d0lc00793eISI: 000592314900002PubMedID: 33169747Scopus ID: 2-s2.0-85096886096OAI: oai:DiVA.org:kth-285877DiVA, id: diva2:1500190
Note

QC 20201216

Available from: 2020-11-11 Created: 2020-11-11 Last updated: 2025-02-09Bibliographically approved
In thesis
1. Microfluidic Compartmentalization for Smart Materials, Medical Diagnostics and Cell Therapy
Open this publication in new window or tab >>Microfluidic Compartmentalization for Smart Materials, Medical Diagnostics and Cell Therapy
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
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., 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 Pharmaceutical and Medical Biotechnology Nano Technology
Identifiers
urn:nbn:se:kth:diva-307246 (URN)978-91-8040-105-0 (ISBN)
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: 2025-02-17Bibliographically approved

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Iseri, Emrevan der Wijngaart, Wouter

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