Le système immunitaire adaptatif joue un rôle de premier plan dans la défense contre les infections. La réponse humorale, impliquant la production d'anticorps, est un élément important de la réponse immunitaire adaptative. Au cours d'une infection, des cellules B spécifiques du système immunitaire prolifèrent et libèrent de grandes quantités d'anticorps qui se lient sélectivement à la protéine cible (antigène) trouvée sur le pathogène invasif, induisant la destruction du pathogène.Cependant, le système immunitaire ne répond pas toujours suffisamment efficacement pour détruire les agents pathogènes, et les mécanismes de tolérance empêchent la génération d'anticorps contre les protéines humaines - comme les marqueurs de surface cellulaire sur les cellules cancéreuses ou les cytokines impliquées dans des maladies inflammatoires et auto-immunes - qui pourraient être des cibles thérapeutiques importantes. Par conséquent, il existe un grand intérêt pour la recherche et le développement d'anticorps spécifiques qui peuvent être utilisés pour le traitement des patients par immunothérapie. En raison de leur grande affinité et de leur liaison sélective aux antigènes, les anticorps monoclonaux (mAbs) sont apparus comme des agents thérapeutiques puissants. Les anticorps monoclonaux dérivés de cellules B individuelles ont une séquence unique et présentent une affinité de liaison pour un antigène spécifique. Cependant, jusqu'à maintenant, la découverte des mAbs a été limitée par l'absence de méthodes à haut débit pour le criblage direct et à grande échelle de cellules B primaires non immortalisées pour découvrir les rares cellules B qui produisent des anticorps spécifiques d'intérêt clinique. Ceci est maintenant possible avec l'émergence et l'amélioration des méthodes de compartimentation in vitro pour l'encapsulation et le criblage de cellules uniques dans des gouttelettes picolitriques. Dans mon projet de doctorat, je décris le développement d'immunodosages et de dispositifs microfluidiques pour le criblage phénotypique direct de cellules individuelles à partir de populations de cellules B enrichies. Ce développement a permis une analyse détaillée de la réponse immunitaire humorale, avec une résolution à l’échelle de la cellule unique. C’est aussi un élément essentiel d'un pipeline de détection d'anticorps couplant le criblage phénotypique de cellules individuelles au séquençage d'anticorps sur cellules uniques. Il est maintenant possible, pour la première fois, de cribler des millions de cellules B individuelles en fonction de l'activité de liaison des anticorps sécrétés et de récupérer les séquences d'anticorps / The adaptive immune system plays a leading role in defense against infection. The humoral response, involving the production of antibodies, is an important component of the adaptive immune response. During an infection, specific B cells of the immune system proliferate and release large amounts of antibodies which bind selectively to the target protein (antigen) found on the invading pathogen, inducing destruction of the pathogen. However, the immune system does not always respond efficiently enough to destroy pathogens, and tolerance mechanisms prevent the generation of antibodies against human protein - such as cell surface markers on cancer cells or cytokines involved in inflammatory and autoimmune disease - that could be important therapeutic targets. Hence, there is great interest in research and development of specific antibodies that can be used for immunotherapy of patients. Due to their high affinity and selective binding to antigens, monoclonal antibodies (mAbs) have emerged as powerful therapeutic agents. Monoclonal antibodies derived from single B cells have a unique sequence and display binding affinity for a specific antigen. However, until now, the discovery of mAbs has been limited by the lack of high-throughput methods for the direct and large-scale screening of non-immortalized primary B cells to uncover rare B cells which produce the specific antibodies of clinical interest. This is now becoming possible with the emergence and improvement of in vitro compartmentalization methods for single-cell encapsulation and screening in picoliter droplets. In my PhD project, I describe the development of binding immunoassays and microfluidic devices for the direct phenotypic screening of single-cells from enriched B cell populations. This development has enabled detailed analysis of the humoral immune response, with single-cell resolution and is an essential component of an antibody-discovery pipeline coupling single-cell phenotypic screening to single-cell antibody sequencing. It is now possible, for the first time, to screen millions of single B cells based on the binding activity of the secreted antibodies and to recover the antibody sequences

This dissertation concerns the development, fabrication and integration in a gas sensing microdevice of a novel 3-dimensional (3D) nanostructured metal-oxide semiconducting film that effectively merges the benefits of inorganic nanomaterials with the simplicity offered by non-lithographic electrochemistry-based preparation techniques. The film is synthesized via the porous-anodic-alumina-assisted anodizing of an Al/Nb metal bilayer sputter-deposited on a SiO2/Si substrate and is basically composed of a 200 nm thick NbO2 layer holding an array of upright-standing spatially separated Nb2O5 nanocolumns, being 50 nm wide, up to 900 nm long and of 8109 cm2 population density. The nanocolumns work as semiconducting nano-channels, whose resistivity is greatly impacted by the surface and interface reactions. Either Pt or Au patterned electrodes are prepared on the top of the nanocolumn array using an innovative sensor design realized by means of microfabrication technology or via a direct original point electrodeposition technique, followed by selective dissolution of the alumina overlayer. For gas-sensing tests the film is mounted on a standard TO-8 package using the wire-bonding technique. Electrical characterization of the 3D niobium-oxide nanofilm reveals asymmetric electron transport properties due to a Schottky barrier that forms at the Au/Nb2O5 or Pt/Nb2O5 interface. Effects of the active film morphology, structure and composition on the electrical and gas-sensing performance focusing on sensitivity, selectivity, detection limits and response/recovery rates are explored in experimental detection of hydrogen gas and ammonia. The fast and intensive response to H2 confirms the potential of the 3D niobium-oxide nanofilm as highly appropriate active layer for sensing application. A computer-aided microfluidics simulation of gas diffusion in the 3D nanofilm predicts a possibility to substantially improve the gas-sensing performance through the formation of a perforated top electrode, optimizing the film morphology, altering the crystal structure and by introducing certain innovations in the electrode design. Preliminary experiments show that a 3D nanofilm synthesized from an alternative Al/W metal bilayer is another promising candidate for advanced sensor applications. The techniques and materials employed in this work are advantageous for developing technically simple, cost-effective and environmentally friendly solutions for practical micro- and nanodevices, where the well-defined nano-channels for charge carriers and surface reactions may bring unprecedented benefits.

No description available.

Microfluidics covers the science of manipulating small quantities of fluids using microscale devices with great potential in analysis, multiplexing, automation and high-throughput screening. Compared to conventional systems, microfluidics benefits from miniaturization resulting in shortened time of experiments, decreased sample and reagent consumptions as well as reduced overall costs. For microfluidic devices where further weight and cost reduction is additionally required, stimuli-responsive hydrogels are particularly interesting materials since they can convert an environmental stimulus directly to mechanical work without any extra power source. Hydrogels are used as chemostats, micropumps, and chemo-mechanical valves in microfluidics. Existing studies about hydrogels for flow control reported on hydrogels responsive to only one stimulus, including temperature, pH value, and solvent. Combining temperature and pH stimuli within one material is an interesting approach, which allows internal as well as external flow control and broadens potential applications. Among the variety of temperature- and pH-responsive monomers, N-isopropylacrylamide (NiPAAm) and acrylic acid (AA) are considered as ideal building blocks to obtain a hydrogel with pronounced stimuli response. There are different architectures for realizing a temperature- and pH-responsive hydrogel with NiPAAm and AA (e.g. copolymer gels, interpenetrating polymer networks (IPNs), semi-IPNs, or graft copolymer gels). Each approach has its inherent benefits and disadvantages. Grafted hydrogels with a temperature-responsive backbone and pH-responsive graft chains are a promising architecture overcoming drawbacks of copolymer gels (loss of thermoresponsive behavior due to the comonomer), interpenetrating polymer networks (IPNs, difficult fabrication of structured particles via soft lithography), and semi-IPNs (leakage of penetrating polymer). However, studies about multi-responsive grafted hydrogels for flow control in microfluidics are comparatively rare and further research is needed to emphasize their real potential. For this reason, the overall aim of this work was the synthesis of temperature- and pH-responsive grafted hydrogels based on NiPAAm and AA for flow control in microfluidics. This required the synthesis of a pH-responsive macromonomer by RAFT polymerization. As a suitable chain transfer agent with a carboxylic acid group for an end-group functionalization, 2-(dodecyl-thiocarbonothioylthio)-2-methylpropionic (DTP) acid was employed. The approach towards the synthesis of the pH-responsive macromonomer based on two key steps: (i) attaching a functional group, which retains during RAFT polymerization, and (ii) conducting the RAFT polymerization to synthesize the pH-responsive macromonomer. In total, four functionalizations for the macromonomer were investigated, including allyl, unconjugated vinyl, acrylamide, and styrene. End-group analysis and solubility tests revealed that macromonomers with a styrene functionalization are suitable for the synthesis of graft copolymer gels. A series of grafted net-PNiPAAm-g-PAA-styrene hydrogels with a PNiPAAm backbone and PAA-styrene graft chains (Mn = 4200 g/mol, Mw/Mn = 1.6) were prepared and characterized. The main goal was to identify suitable stimuli for an application as a chemo-mechanical valve and to show reversibility of the swelling and shrinking process. Importantly, the temperature sensitivity should be retained, while a pH response needs to be introduced. Equilibrium swelling studies quantified with the response ratio revealed that a grafting density of PAA-styrene between 0.25 and 1 mol-% provides a suitable response towards temperature, pH, salt, and solvent. Furthermore, the swelling and shrinking process is highly reproducible over four consecutive cycles for all four stimuli. In order to evaluate the swelling kinetics of grafted net-PNiPAAm-g-PAA-styrene hydrogels, the collective diffusion model extended by a volume specific surface was applied. The determined cooperative diffusion coefficients of net-PNiPAAm-g-PAA-styrene indicated faster response time with increasing PAA-styrene content. Remarkably, net-PNiPAAm-g-PAA-styrene containing 1 mol-% PAA-styrene exhibited an accelerated swelling rate by a factor of 9 compared to pure net-PNiPAAm. Rheological analysis of net-PNiPAAm-g-PAA-styrene showed that an increasing graft density leads to decreasing mechanical stability. The photopolymerization experiments showed that the gelation time linearly increases with the grafting density. Grafted net-PNiPAAm-g-PAA-styrene hydrogels were tested in two fluidic setups for flow control. A straightforward fluidic platform was developed consisting of a fluid reservoir, an inlet channel, an actuator chamber and an outlet channel. The actuator chamber was filled with crushed hydrogel particles. Accordingly, the fluid flow was directed by the active resistance of the hydrogel particles in the actuator chamber (i.e. swelling degree) and allowed flow control by the local environmental conditions. Flow rate studies showed that the fluid flow throttles when the inlet channel was provided with a solution in which the hydrogel swells (pH 9 buffer solution at room temperature). In contrast, the hydrogel-based valve opens immediately when a solution was used in which the hydrogel collapses. The advantageous properties of net-PNiPAAm-g-PAA-styrene were highlighted by using pH, salt and solvent stimulus in one experiment. Remarkably, the opening and closing function was reversible over six consecutive cycles. As part of a collaboration project with the chair of polymeric microsystems within the Cluster of Excellence Center for Advancing Electronics Dresden (A. Richter and P. Frank), membrane assures hydraulic coupling in a chemo-fluidic membrane transistor (CFMT) and grafted net-PNiPAAm-g-PAA-styrene hydrogels were combined to emphasize the potential of both systems. Flow rate studies showed that 4 different stimuli can be used to control the opening and closing state of the CFMT. Multiple opening and closing cycles revealed no considerable changes in the valve function emphasizing a high potential for an application in microfluidics.

Models using 3D cell culture techniques are increasingly accepted as the most biofidelic in vitro representations of tissues for research. These models are generated using biomatrices and bulk populations of cells derived from tissues or cell lines. This thesis study focuses on an alternate method to culture individually selected cells in relative isolation from the rest of the population under physiologically relevant matrix conditions. Matrix gel islands are spotted on a cell culture dish to act as support for receiving and culturing individual single cells; a glass capillary-based microfluidic setup is used to extract each desired single cell from a population and seed it on top of an island. Using examples of breast and colorectal cancers, we show that individual cells evolve into tumors or aspects of tumors displaying different characteristics of the initial cancer type and aggressiveness. By implementing a morphometry assay with luminal A breast cancer, we demonstrate the potential of the proposed approach to studying phenotypic heterogeneity. Results reveal that intertumor heterogeneity increases with time in culture and that varying degrees of intratumor heterogeneity may originate from individually seeded cells. Moreover, we observe a positive correlation between fast-growing tumors and the size and heterogeneity of their nuclei.

In dieser Arbeit wird eine neue Methode und ein neuartiges FET -Sensorelement zum Nachweis von Flüssigkeitsbewegungen vorgestellt, das zudem bei Bedarf auch als Chemo- oder Biosensor fungieren kann. Das Einsatzspektrum von FET-basierten Sensoren in Lab on a Chip-Systemen wird dadurch entscheidend erweitert. Bei dem entwickelten FET-Sensor Bauelement handelt es sich um einen normally-on n-leitenden Dünnschichtfeldeffekttransistor mit Ti-Au-Kontakten, basierend auf Silicon-on-Insulator- Substraten, wobei das natürliche Oxid des Siliziumfilms als Schnittstelle zum Elektrolyten bzw. zur Flüssigkeit verwendet wird. Der mit 10exp16 Bor Atomen pro cm³ p-dotierte Siliziumdünnfilm hat eine Dicke von nur 55 nm und ist durch eine 95 nm dicke Siliziumdioxidschicht vom darunterliegenden Siliziumsubstrat von 600 µm Dicke elektrisch isoliert. Aufgrund der geringen Schichtdicke durchdringt die feldempfindliche Raumladungs- bzw. Verarmungszone die gesamte Dünnschicht, so dass durch Anlegen einer Backgatespannung am Substrat der spezifische Widerstand und die Empfindlichkeit des Bauelements eingestellt werden können. Grundlegende ISFET-Funktionalitäten wie die Empfindlichkeit auf Änderungen der Ionenstärke und des pH-Wertes werden nachgewiesen und ein ENFET-Glukosesensor realisiert. Zudem wird im Hinblick auf die Separation von Emulsionen der Nachweis erbracht, dass die Benetzung mit Hexan und Toluol eine Änderung der spezifischen Leitfähigkeit bewirkt, und die Empfindlichkeit des Bauelements nach Beschichtung mit einem hydrophoben Methacrylatcopolymerfilm erhalten bleibt. Hinsichtlich der Verwendung des FET-Sensor Bauelements zum Nachweis von Flüssigkeitsbewegungen wird zunächst ein theoretisches Modell entwickelt, dessen Kernaussage ist, dass sich in einem rechteckigen Kanal der relative Bedeckungsgrad mit Flüssigkeit direkt proportional zum Drainstrom des FET-Sensors verhält. Basierend auf diesem theoretischen Modell, welches experimentell belegt wird, können mittels eines einzelnen FET-Sensors Füllstand und Füllgeschwindigkeit bzw. bei bekannter Füllgeschwindigkeit Kapillarvolumen und Kapillargeometrie bestimmt werden. Abweichungen von der direkten Proportionalität erlauben zudem, Rückschlüsse auf die Benetzungseigenschaften der Kapillaren und die Dynamik an der Halbleitergrenzfläche zu ziehen. Ist ein Sensorelement vollständig mit Flüssigkeit bedeckt, wird mittels Lösungsmitteltropfen als Markerobjekten die Strömungsgeschwindigkeit bestimmt. Ändert sich die Ionenkonzentration im Elektrolyten als Funktion der Strömungsgeschwindigkeit, so kann die Strömungsgeschwindigkeit durch Messung der Ionenkonzentration mittels FET-Sensor ebenfalls ermittelt werden. Als wichtigster Demonstrator für die Verwendung des FET-Sensors wird ein komplexes Lab on a Chip-System zur Separation von Emulsionen auf chemisch strukturierten Oberflächen entwickelt, bei dem der Separationsvorgang mittels FET-Sensorarray verfolgt werden kann. Zur einfachen Herstellung chemisch modifizierter Oberflächen für die Separationsexperimente werden die Abscheidung von nanoskaligen hydrophoben Methacrylatcopolymerfilmen und die selektive Fluorsilanisierung von Oberflächen sowie deren Lösungsmittelbeständigkeit in Wasser, Toluol und Aceton untersucht. Dabei zeigt sich, dass die Hydrophobie nach Lösungsmittelbehandlung weitestgehend erhalten bleibt, Wasserrückstände im Methacrylatfilm aber zu einer reversiblen Schichtdegradation führen können. Als Modellsystem werden Hexan-Wasser- bzw. Toluol-Wasser-Emulsionen verwendet, die auf Oberflächen getrennt werden, deren eine Seite hydrophil, und deren andere Seite hydrophob ist (Stufengradient). Der Separationsprozess beruht auf der großen Affinität des Wassers hin zu polaren Oberflächen, wobei das wenig selektive Lösungsmittel zur unpolaren Seite gedrängt wird. Zur Erlangung eines tieferen Verständnisses des Prozesses werden die Tropfenkoaleszenz und der Einfluss geometrischer Beschränkungen untersucht. Die Versuche werden sowohl auf offenen Oberflächen als auch im Spalt, unter Verwendung von hydrophilen und hydrophoben Oberflächen, durchgeführt. Es zeigt sich, dass sich die Dynamik der Tropfenkoaleszenz im Spalt umgekehrt zur Dynamik auf offenen Oberflächen verhält. Dies wird mittels eines hierzu entwickelten theoretischen Modells erklärt, welches die Minimierung der Oberflächenenergie und Hystereseeffekte einbezieht. Das Lab on a Chip-System schließlich besteht aus einem mit Siliziumnitrid beschichteten FET-Sensorchip, auf den eine Separationszelle aufgeklebt ist. Neben dem Einlass für die Emulsion ist ein weiterer Einlass vorhanden, durch den Salzsäure für eine pH-Reaktion zugegeben werden kann. Der gesamte Separationsprozess sowie die anschließende pH-Reaktion, lassen sich bequem am PC anhand der Änderung der Stromstärke der einzelnen Sensoren verfolgen und analysieren. Wichtige Ergebnisse hier sind: 1) Mittels eines quasi 1-dimensionalen Sensorarrays kann der Verlauf einer Flüssigkeitsfront in einem 2-dimensionalen Areal überwacht bzw. dargestellt werden. 2) Anhand der Signatur des Signalverlaufs bei pH-Änderung und Flüssigkeitsbewegung, können beide Prozesse unterschieden werden. Der Sensor kann also zum Nachweis von Flüssigkeitsbewegungen und zugleich als Chemosensor eingesetzt werden. Es wurde also nicht nur ein neuartiges, äußerst robustes, chemikalienbeständiges und biokompatibles Multifunktionssensorelement mit Abmessungen im Mikrometer- bis Millimeterbereich entwickelt, sondern auch eine neue Methode entwickelt, mit der es möglich ist, sowohl (bio-)chemische Reaktionen als auch die Bewegung von Flüssigkeiten in Lab on a Chip-Systemen nachzuweisen.

Switchable hydrogel-layered composite membranes can be used for the analysis of particle size distributions. This functionality is provided by pores with controllable diameter. In order to obtain a device that can be used to measure the cell size distribution in native biological samples, lots of switchable pores are required. In the current work, we model and simulate the mechanical behavior of active composite membranes with switchable pores. This is done in order to find the maximum number of pores that can be integrated into a membrane without cross-influencing effects on the actuation of the pores. Therefore, we investigate (1) the interaction of active pores inside the multifunctional composite and (2) the membrane bending under microfluidic pressure load. We show that through miniaturization, sufficient pores can be added to a permeation control membrane for processing native blood samples. The envisioned device allows a parallelized measurement of cell sizes in a simple lab-on-a-chip setup.

Membranes act as smart structures in respect to their permeation abilities. Control of particle and fluid permeation through a synthetic membrane can be achieved by using different effects like size-exclusion or electromagnetic interactions that occur between the particles and membrane pores. The simulation of controlled permeability provides an insight into the smart behavior of membranes for chemical signal processing, sensing interfaces or lab-on-a-chip devices. In the current work, we model the underlying physical processes on a microfluidic level using the engineer’s approach of laminar flow through pipes. Different pore geometries inside a composite membrane system consisting of a polyethylene terephthalate support membrane and a poly(N-isopropylacrylamide) hydrogel-layer are investigated. Simulations for different states of thermally induced pore opening are performed for free and blocked states. From the results we derive paradigms for the design of a membrane system for microfluidic cell-size profiling considering stimulus-range, pore shape and measurement setup.

Ce travail est dédié à l'étude d'écoulement diphasique sous pression en micro et milli-capillaires pour permettre la mesure efficace de propriétés de mélanges sous pression. Dans un premier temps, un montage expérimental comprenant un micro-dispositif pour des applications allant jusqu'à des pressions de 25 MPa a été développé. Ce micro-dispositif à faible coût et transparent, permet la visualisation de l'écoulement grâce à une caméra rapide. Dans un second temps, l'étude du système diphasique du système CO2 supercritique / liquide ionique (1-Butyl-3-Methyl-Imidazolium hexafluorophosphate, [BMIm][PF6]) sous pression est présentée. L'écoulement est réalisé dans des tubes cylindriques de silice de diamètre intérieur de 536 micromètres. Parmi les différents régimes d'écoulements diphasiques, nous nous sommes intéressés aux écoulements périodiques intermittents ou « Taylor flow ». La zone de conditions opératoires couvertes est la suivante : [308 K - 318 K] x [9 MPa - 18 MPa]. Les films de la caméra rapide sont traités par analyse d'image. Le logiciel« μcap2phase » développé pour traiter les films permet d'accéder aux caractéristiques géométriques de l'écoulement (volume et aire de chaque phase, longueur du motif, longueur de la phase dispersée et vitesse de la phase dispersée). Un comportement atypique est observé avec ce binaire. En effet le transfert unidirectionel du CO2SC dans le [BMIm][PF6] induit des changements importants des propriétés physico-chimiques de la phase continue : abaissement de la viscosité (divisée par 10) et augmentation de la masse volumique (multiplié par 1,5). Ces changements impliquent une modification de la forme et de la taille des bulles au cours de l'écoulement. Une importante vitesse de glissement a été identifiée. Elle est générée par la présence d'un film épais de viscosité plus élevée au niveau des parois du capillaire. Un modèle de transfert de matière prenant en compte certaines des observations expérimentales (variations de la taille du film, de la taille des bulles, et des propriétés de la phase continue tout au long du capillaire) a été développé. Ce modèle intégrera dans le futur la tension interfaciale bulle/phase continue et le facteur de forme de la bulle. / The present work deals with the study of two-phase flow in micro-capillaries under high-pressure to enhance properties measurements. As a first step, an experimental setup consisting of a micro-device has been developed for microfluidics high-pressure applications (P < 25 MPa). The set-up combines good optical access, high-pressure resistance, homogeneous operating conditions, fast process control and detection, and the ability to generate a stable two-phase flow. In the following step, we focused our work on the hydrodynamics features of two-phase flow between supercritical carbon dioxide(SC-CO2) and ionic liquid (1-butyl-3-methyl-imidazolium hexafuorophosphate) ([BMIm][PF6]) .The two-phase flow system is observed with a high-speed camera. The flow is conducted in silica capillary tubing with inner diameter of 536 micrometers. Among the two-phase flow patterns, ours relates to Taylor flow. The range of operating conditions are : [308 K - 318 K] x [9 MPa - 18 MPa]. An image analysis home-made soft, « μcap2phase », has been developed in order to access to the geometric properties and to the velocities of the dispersed phase from images. The two-phase flow presents an unexpected behaviour. In fact, the unidirectional transfer of SC-CO2 in [BMIm][PF6] induces significant changes in physico-chemical properties of continous phase : viscosity decreases(divided by ten) and density increases (1.5 fold). Due to the wide variations of the continuous phase properties along the capillary, size and shape of the dispersed phase bubbles are simultaneously modified. A significant slip velocity has been indentified located between a thick liquid film (at the wall of capillary) and a Taylor flow region (at the center). A mass transfer taking into account some experimental observations (changes in film thickness, in bubble size, and in properties of the continuous phase throughout the capillary) is developed. Further, this model will integrate the interfacial tension between bubbles and continous phase.

År 2020 listade Världshälsoorganisationen (WHO) cancer som den globalt ledande dödsorsaken med över 10 miljoner dödsfall årligen. Av dessa 10 miljoner fall förekommer nästan 70% i låg- till medelinkomstländer - en siffra som på grund av den låga prioriteringen av cancerbehandling- och diagnostik förväntas öka till 85% redan år 2030. Att utveckla enkla, specifika och prisvärda verktyg för diagnostik kommer därför att bli avgörande för förebyggandet av cancer på en global nivå. För att komma ett steg närmare denna utveckling optimerades och testades i denna studie ett mikrofluidiskt system, utvecklat genom layer-bylayer- metoden, baserat på cellulosa nanofibriller med förmågan att isolera och fånga cirkulerande tumörceller. För att uppnå en termodynamisk jämvikt optimerades systemets hydrodynamiska parametrar optimerades för att uppnå en homogen fördelning med hög densitet av det cellulosa-baserade systemet i det mikrofluidiska chippet. Då jämvikt är grundläggande för att maximera det efterföljande beläggningen av antikroppar, och därmed hur effektivt celler isoleras, modifierades parametrar såsom koncentration, flödeshastighet, inkubationstid med fler tills att önskad effekt uppnåtts. Således koncepttestades systemet genom att fånga celler spetsade i blod och därmed demonstrera att systemet kan användas i syfte att isolera cancerceller från blodprov. Detta öppnar upp för utveckling av liknande diagnostiska verktyg som kan användas för att isolera lågfrekventa celler direkt från blod. / In 2020, the World Health Organization (WHO) listed cancer as the leading cause of death worldwide, reaching a staggering number of 10 million cancer-related deaths annually. Of these 10 million deaths, nearly 70% occurred in low- and middle-income countries; a number that is expected to increase to 85% by 2030 due to the lack of resources as well as low priority of the development of cancer treatment and diagnosis. Hence, the development of a sophisticated, specific and affordable diagnostic tool will be crucial for global cancer prevention and control. In this study, a cellulose nanofibril-based Layer-by-Layer system for immuno-capture of tumour cells in a microfluidic device was optimized and tested for the development of a simple and cost-effective diagnostic tool for use in resource-limited areas. In the pursuit of a thermodynamic equilibrium, the hydrodynamic parameters of the system were optimized to achieve a homogeneous distribution with a high surface density of the cellulose-based system across the microfluidic channels. Since an equilibrated system is essential to maximize the antibody coating, and thereby cell capture efficiency, parameters including but not limited to concentration, flow rate and incubation time were altered until a desired effect had been achieved. Thus, as proof-of-concept, the system was tested by capturing cancer cells spiked into whole blood, thereby demonstrating that the system can be utilized for the purpose of isolating cancer cells from blood samples. This paves the way for the development of similar clinical diagnostic tools for the isolation of rare cells directly from whole blood.