Confronted with the global demographic changes and the increasing pressure on modern healthcare system, there has been a surge of developing new technology platforms in the past decades. Droplet microfluidics is a prominent example of such technology platforms, which offers an efficient format for massively parallelized screening of a large number of samples and holds great promise to boost the throughput and reduce the costs of modern biomedical activities. Despite recent achievements, the realization of a compact and generic screening system which is suited for resource-limited settings and point-of-care applications remains elusive. To address the above challenges, the dissertation focuses on the development of a compact multifunctional droplet micro-magnetofluidic system by exploring the advantages of magnetic in-flow detection principles. The methodologies behind a novel technique for biomedical applications, namely, magnetic in-flow cytometry have been put forth, which encompass magnetic indexing schemes, quantitative multiparametric analytics and magnetically-activated sorting. A magnetic indexing scheme is introduced and intrinsic to the magnetofluidic system. Two parameters characteristic of the magnetic signal when detecting magnetically functionalized objects, i.e. signal amplitude and peak width, providing information which is necessary to perform quantitative analysis in the spirit of optical cytometry has been proposed and realized. Magnetically-activated sorting is demonstrated to actively select individual droplets or to purify a population of droplets of interest. Together with the magnetic indexing scheme and multiparametric analytic technique, this functionality synergistically enables controlled synthesis, quality administration and screening of encoded magnetic microcarriers, which is crucial for the practical realization of magnetic suspension arrays technologies. Furthermore, to satisfy the needs of cost-efficient fabrication and high-volume delivery, an approach to fabricate magnetofluidic devices on flexible foils is demonstrated. The resultant device retains high performance of its rigid counterpart and exhibits excellent mechanical properties, which promises long-term stability in practical applications.

In novel drug delivery system, the encapsulation of therapeutic cells in microparticles has great promises for the treatment of a range of health con- ditions. Therefore, the encapsulation material and technology are of great importance to the validity and efficiency of the advanced medical therapy. Several unsolved challenges in regards to versatile microparticle synthesis ma- terials and methods form the main obstacle for a translation of novel cell therapy concepts from research to clinical practice. Thiol-ene based polymer systems have emerged and gained great popular- ity in material development in general and in biomedical applications specif- ically. The thiol-ene platform is broad and therefore of interest for a variety of applications. At the same time, many aspects of this material platform are largely unexplored, for example material and manufacturing technology developments for microfluidic applications . In this Ph.D. thesis, thiol-ene materials are explored for use in cell encap- sulation. The marriage of these two technology fields breeds the possibility for a novel microfluidic cell encapsulation approach using a novel encapsulation material. To this end, several new manufacturing technologies for thiol-ene and thiol-ene-epoxy droplet microfluidic devices were developed. Moreover, core-shell microparticle synthesis for cell encapsulation based on a novel co- synthesis concept using a thiol-ene based material was developed and inves- tigated. Finally, a thiol-ene-epoxy system was also used for the formation of microwells and microchannels that improve protein analysis on microarrays. The first part of the thesis presents the background and state-of-the-art technologies in regards to cell therapy, microfluidics, and thiol-ene based ma- terials. In the second part of the thesis, a novel manufacturing approach of thiol-ene-epoxy material as well as core-shell particle co-synthesis in micro- fluidics using thiol-ene based material are presented and characterized. The third part of the thesis presents the cell viability studies of encapsulated cells using the novel encapsulation material and method. In the final part of the thesis, two applications of thiol-ene-epoxy gaskets for protein detection mi- croarrays are presented. / Inkapsling av levande celler i mikrokapslar för terapeutiska ändamål är mycket lovande för frmatida behandling av många olika sjukdomar. Emeller- tid är en behandlings effektivitet i hög grad beroende av vilka material som används för inkapsling och vilken teknisk lösning som används för att ska- pa mikrokapslarna. För närvarande återstår det många utmaningar för att omvandla grundforskningresultat till klinisk verklighet, vilken kräver mer än- damålsenliga tillvägagångssätt för att tillverka mikrokapslar i material som är kompatibla med användningsområdena. De senaste åren har tiol-en baserade polymerer har blivit mycket använda för materialutveckling i stort och för biomedicinska tillämpningar i synnerhet. Med tiol-en kemi kan en mycket stor mängd helt olika syntetiska material framställas, vilket gör tiol-ener intressanta för en mängd applikationer. För närvarande är dock mycket inom denna materialklass outforskat, t.ex. inom material och tillverkningmetodik för mikrofluidiktillämpningar. I denna avhandling används tiol-ener för cellinkapsling. Sammanslagning av dessa teknologier möjliggör en ny typ av cellinkapsling med nya materi- alegenskaper. En mängd olika tillverkningssätt där tiol-en eller tiol-en-epoxi används för droplet-mikrofluidiksystem utvecklades. Core-shell mikrokapsel- syntes för cell-inkapsling baserat på en ny metod för samtidig syntes av både core och shell utvecklades och karaktäriserades. Slutligen utvecklades ett tiol- en-epoxi system för enkel integrering med proteinmikroarrayer på objektsglas. I avhandlingens första del presenteras bakgrund och dagens bästa teknolo- gier för terapeutisk cellinkapsling, mikrofluidik och tiol-en baserade material. I avhandlingens andra del presenteras en ny tillverkningsmetod för mikro- strukturerade tiol-en-epoxi artiklar och samtidig syntes av core och shell för mikrokapslar med användande av mikrofluidik. I den tredje delen presenteras cellöverlevandsstudier för de celler som inkapslats med de nya materialen och de nyutvecklade metoderna. I den avslutande delen beskrivs två specifika fall där tiol-en-epoxi komponenter används för proteindetektion och mikroarrayer. / <p>QC 20171122</p>

The research work focuses on optimizing various parameters for controlling cells using negative dielectrophoresis and entrapping them in droplet microfluidics. This is achieved by developing a conductivity medium, combining CytoRecovery, BSA, and EDTA, to maintain a steady count of single cells with good viability over an extended period. The study involves the optimization of frequency and voltage applied to the electrodes to achieve the desired dielectrophoretic forces for long-term cell manipulation. The optimization is based on simulations performed using myDEP and COMSOL software. Additionally, the stability of the conductivity medium is tested during prolonged electric field applications. Considering the significance of working with cells, ensuring the temperature inside the channels remains within physiological limits is vital. Both COMSOL simulations and physical experiments using Rhodamine B dye are conducted to achieve this objective. Moreover, a well-designed process flow is proposed for performing cellular entrapment in droplets. Finally, a novel microfluidic cleaning protocol has been developed to efficiently eliminate both non-biological and biological contaminants from the microfluidic chamber. This innovative protocol has the potential to enable the reuse of any microfluidic chip that does not possess a functionalized surface. / Forskningsarbetet fokuserar på att optimera olika parametrar för att kontrollera celler med hjälp av negativ dielektrofores och fånga in dem i droppmikrofluidik. Detta uppnås genom att utveckla ett konduktivitetsmedium, som kombinerar CytoRecovery, BSA och EDTA, för att upprätthålla ett jämnt antal enstaka celler med god livsduglighet under en längre period. Studien involverar optimering av frekvens och spänning som appliceras på elektroderna för att uppnå de önskade dielektroforetiska krafterna för långvarig cellmanipulation. Optimeringen är baserad på simuleringar utförda med mjukvaran myDEP och COMSOL. Dessutom testas konduktivitetsmediets stabilitet under långvariga elektriska fälttillämpningar. Med tanke på betydelsen av att arbeta med celler är det viktigt att se till att temperaturen inuti kanalerna håller sig inom fysiologiska gränser. Både COMSOL-simuleringar och fysiska experiment med Rhodamine B-färgämne genomförs för att uppnå detta mål. Dessutom föreslås ett väldesignat processflöde för att utföra cellulär infångning i droppar. Slutligen har ett nytt mikrofluidrengöringsprotokoll utvecklats för att effektivt eliminera både icke-biologiska och biologiska föroreningar från mikrofluidkammaren. Detta innovativa protokoll har potential att möjliggöra återanvändning av alla mikrofluidiska chip som inte har en funktionaliserad yta.

Confronted with the global demographic changes and the increasing pressure on modern healthcare system, there has been a surge of developing new technology platforms in the past decades. Droplet microfluidics is a prominent example of such technology platforms, which offers an efficient format for massively parallelized screening of a large number of samples and holds great promise to boost the throughput and reduce the costs of modern biomedical activities. Despite recent achievements, the realization of a compact and generic screening system which is suited for resource-limited settings and point-of-care applications remains elusive. To address the above challenges, the dissertation focuses on the development of a compact multifunctional droplet micro-magnetofluidic system by exploring the advantages of magnetic in-flow detection principles. The methodologies behind a novel technique for biomedical applications, namely, magnetic in-flow cytometry have been put forth, which encompass magnetic indexing schemes, quantitative multiparametric analytics and magnetically-activated sorting. A magnetic indexing scheme is introduced and intrinsic to the magnetofluidic system. Two parameters characteristic of the magnetic signal when detecting magnetically functionalized objects, i.e. signal amplitude and peak width, providing information which is necessary to perform quantitative analysis in the spirit of optical cytometry has been proposed and realized. Magnetically-activated sorting is demonstrated to actively select individual droplets or to purify a population of droplets of interest. Together with the magnetic indexing scheme and multiparametric analytic technique, this functionality synergistically enables controlled synthesis, quality administration and screening of encoded magnetic microcarriers, which is crucial for the practical realization of magnetic suspension arrays technologies. Furthermore, to satisfy the needs of cost-efficient fabrication and high-volume delivery, an approach to fabricate magnetofluidic devices on flexible foils is demonstrated. The resultant device retains high performance of its rigid counterpart and exhibits excellent mechanical properties, which promises long-term stability in practical applications.