Umeå University's logo

Diseases caused by pathogenic agents such as bacteria and viruses result in devastating costs on personal and societal levels. However, it is not just the emergence of new diseases that is problematic. Antibiotic resistance among bacteria makes uncomplicated infections difficult and lethal. Resilient disease-causing spores spread in hospitals, the food industry, and water supplies requiring effective detection and disinfection methods. Further, we face complex neurological diseases where no effective treatment or diagnostic methods exist. Thus, we must increase our fundamental understanding of these diseases to develop effective diagnostic, detection, disinfection, and treatment methods.

Classically, the methods used for detecting and studying the underlying mechanics of pathogenic agents work on a large scale, measuring the average macroscopic behavior and properties of these pathogens. However, just as with humans, the average behavior is not always representative of individual behavior. Therefore, it is also essential to investigate the characteristics of these pathogens on a single cell or particle level. 

This thesis develops and applies optical techniques to characterize pathogenic biomaterial on a single cell or particle level. At the heart of all these studies is our Optical Tweezers (OT) instrument. OT are a tool that allows us to reach into the microscopic world and interact with it. Finally, by combining OT with other experimental techniques, we can chemically characterize biomaterials and develop assays that mimic different biological settings. Using these tools, we investigate bacterial adhesion, disinfection, and detection of pathogenic spores and proteins.

Hopefully, the insights of these studies can lessen the burden on society caused by diseases by helping others develop effective treatment, diagnostic, detection, and disinfection methods in the future. 

Biophysics bridges the research questions of biology with the measurement techniques of physics and engineering. Through collaborations with industrial and academic researchers across multiple disciplines, the studies presented in this thesis address a wide range of biological phenomena, from the minute thermal motion of single-cell microorganisms to the flow conditions in industrial and natural environments. The ability of biophysics to operate across these scales enables applications including pathogen detection, biofilm prevention, and personalized medicine. However, advancing research in these areas requires sophisticated instruments that are often slow and costly to produce using conventional manufacturing techniques.

This thesis explores how recent advances in open-source electronics and consumer-grade additive manufacturing, known as 3D printing, can be used for rapid prototyping of custom scientific instruments in the lab. The thesis details a practical framework for designing instruments using additive manufacturing, computer simulations, and integrated measurement systems, including design principles for improved performance and reliability. The work covers instruments for single-cell detection, manipulation, and disruption using microscopy and microfluidics, with the aim of increasing measurement throughput. It also presents flow devices for enhanced biofilm incubation, fluid biomimicry, and clinical assessment of cerebral fluid dynamics. Throughout the development process, emphasis is placed on extending measurement capabilities beyond those offered by standardized methods and commercial systems, while also providing the analytical tools needed to interpret the measurement results.

Together, this work demonstrates that consumer-grade 3D printers can produce components with sufficient precision and accuracy for advanced biophysical instrumentation, enabling a more collaborative and demand-driven approach to instrument development within the research community.

Biofysik förenar biologins forskningsfrågor med de mätmetoder och tekniska lösningar som utvecklats inom fysik och ingenjörsvetenskap. Genom samarbeten med industriella och akademiska forskare från flera olika discipliner behandlar studierna i denna avhandling ett brett spektrum av biologiska fenomen, från de ytterst små termiska rörelserna hos mikroorganismer till flödesförhållanden i såväl industriella som naturliga miljöer. Biofysikens förmåga att verka över dessa olika skalor möjliggör tillämpningar inom bland annat detektion av skadliga patogener, förebyggande av biofilmsbildning, och individanpassad medicin. Samtidigt kräver forskning inom dessa områden avancerad instrumentering som ofta är både kostsam och tidskrävande att utveckla med konventionella tillverkningsmetoder.

I denna avhandling undersöks hur de senaste framstegen inom elektronik och konsumentinriktad additiv tillverkning, så kallad 3D-utskrift, kan användas för att snabbt utveckla skräddarsydda vetenskapliga instrument i laboratoriemiljö. Avhandlingen presenterar ett praktiskt ramverk för utvecklingen av instrument baserat på additiv tillverkning, datorsimuleringar, och integrerade mätsystem, inklusive designprinciper för förbättrad prestanda och tillförlitlighet. Arbetet omfattar instrument för detektion, manipulering och destruktion av enskilda celler med hjälp av mikroskopi och mikrofluidik, med målet att öka analyskapaciteten. Vidare presenteras flödessystem för förbättrad odling av biofilmer, modeller av biologiska system, och klinisk bedömning av flöden genom hjärnvävnad. Genom hela utvecklingsprocessen har fokus legat på att utöka mätmöjligheterna bortom vad standardiserade metoder och kommersiella system erbjuder, samtidigt som analytiska verktyg utvecklats för att granska insamlat mätresultat.

Sammantaget visar detta arbete att konsumentklassade 3D-skrivare kan tillverka komponenter med den precision och noggrannhet som krävs för avancerad biofysikalisk instrumentering. Därmed möjliggörs en mer samarbetsinriktad och behovsstyrd utveckling av instrument inom forskarsamhället.