Capillary driven devices for patient-centric diagnostics

Lateral flow assays is an example of a successful microfluidic platform relying on passive fluid transport, making them suitable for patient-centric and point-of-care applications. Flow control and valving in capillary driven devices typically rely on design-imprinted functions and operations which can be a limiting factor. This thesis explores dissolvable polymer valves in capillary driven microfluidic systems, a novel type of valves with a timing function. The dissolvable valve technology was used to develop autonomous operations in lamination-based polymer microfluidic systems such as sequential reagent delivery, reagent release and volume-metering, and further utilizes this technology in the Dried Blood Spot (DBS) and Dried Plasma Spot applications described below. Lamination technology is suitable for the integration of the water-dissolvable polymer layers and allows upscaling at a relatively low cost. Advances in the development of LC-MS/MS systems enable the quantification of analytes in microliter-sized blood samples such as DBS. This makes DBS sampling a minimally invasive alternative to venous blood sampling with logistical and ethical advantages for users and health care providers. Unknown sample volume, spot inhomogeneity and hematocrit-related issues have been an obstacle for a wider acceptance of DBS sampling technology. To address these issues, a novel blood-sampling device, the microfluidic DBS card, has been developed within this thesis. The device function is based on capillary driven volume-metering and allows accurate and user independent collection of microliter-sized DBS, directly from a finger-prick. The microfluidic DBS card could help to eliminate some of the issues related to DBS sampling and contribute to a wider acceptance of the technology. Usability and reliability have been considered during the development to enable testing of the microfludic DBS card in a pre-clinical setting. For many analytes and biomarkers, conventional blood sample analysis is performed on plasma or serum samples. This thesis further discusses the use of capillary driven plasma separation based on commercially available asymmetric filtration membranes and capillary driven flow in microchannels. A novel concept for hematocrit and input-volume-independent collection of a 11.6~µl plasma sample from a single drop of blood is demonstrated. The plasma sample is automatically transferred to a sample collection pad forming a Dried Plasma Spot. This could be the next generation of dried sample matrix, enabling an accurate quantification of analytes in Dried Plasma Spots.QC 20180910