From Lab to Chip – and back Polymer microfluidic systems for sample handling in point-of-care diagnostics

University dissertation from Stockholm : KTH Royal Institute of Technology

Abstract: This thesis contributes to the development of Lab-on-a-Chip systems that enables reliable, rapid medical diagnostics at the point-of-care. These contributions are focused on microfluidic Lab-on-a-Chip systems for sepsis diagnosis, autonomous sample-to-answer tests, and dried blood spot sampling.Sepsis is a serious condition with high mortality and high costs for society and healthcare. To facilitate rapid and effective antibiotic treatment, improved sepsis diagnostics is needed. Diagnosis of sepsis requires the processing of relatively large blood volumes, creating a need for novel and effective techniques for the handling of large volume flows and pressures on chip. Components, materials, and manufacturing methods for pneumatically driven Lab-on-a-Chip systems have therefore been developed in this thesis. Microvalves, an essential component in many Lab-on-a-Chip systems have been the focus on several of the advances: a novel elastomeric material (Rubbery Off-Stoichiometric-Thiol-Ene-Epoxy) with low gas and liquid permeability; the first leak-tight vertical membrane microvalves, allowing large channel cross-sections for high volumetric flow throughput; and novel PDMS manufacturing methods enabling their realization. Additionally, two of the new components developed in this thesis focus on separation of bacteria from blood cells based on differences in particle size, and cell wall composition: inertial microfluidic removal of large particles in multiple parallel microchannels with low aspect ratio; and selective lysis of blood cells while keeping bacteria intact. How these components, materials and methods could be used together to achieve faster sepsis diagnostics is also discussed.Lab-on-a-Chip tests can not only be used for sepsis, but have implications in many point-of-care tests. Disposable and completely autonomous sampleto- answer tests, like pregnancy tests, are capillary driven. Applying such tests in more demanding applications has traditionally been limited by poor material properties of the paper-based products used. A new porous material, called “Synthetic Microfluidic Paper”, has been developed in this thesis. The Synthetic Microfluidic Paper features well-defined geometries consisting of slanted interlocked micropillars. The material is transparent, has a large surface area, large porous fraction, and results in low variability in capillary flowrates. The fact that Synthetic Microfluidic Paper can be produced with multiple pore sizes in the same sheet enables novel concepts for self-aligned spotting of liquids and well-controlled positioning of functional microbeads.Diagnostic testing can also be achieved by collecting the sample at the point-of-care while performing the analysis elsewhere. Easy collection of finger-prick blood in paper can be performed by a method called dried blood spots. This thesis investigates how the process of drying affects the homogeneity of dried blood spots, which can explain part of the variability that has been measured in the subsequent analysis. To reduce this variability, a microfluidic sampling chip has been developed in this thesis. The chip, which is capillary driven, autonomously collects a specific volume of plasma from a drop of blood, and dry-stores it in paper. After sampling, the chip can be mailed back to a central lab for analysis.