Precise sample metering method by coordinated burst action of hydrophobic burst valves applied to dried blood spot collection

Dried blood spot (DBS) sampling by finger-pricking has recently gained a lot of interest as an alternative sample collection method. The reduced invasiveness, requirement of lower sample volumes and suitability for long-term storage at room temperature make DBS ideal for use in home settings or low-resource environments. However, traditional protocols often suffer from biased analysis data due to variable and not exactly known blood volumes present in the samples. In this work, a novel device has been developed to split-off precisely metered volumes from a blood drop and load them on pre-cut filter paper. Hereto, hydrophobic burst valves (HBV) were developed to temporarily retain a fluid flow, configurable to burst at pressures within a range of 175-600 Pa. By combining HBVs with different burst pressures, a volume metering system was developed to allow parallel metering of multiple pre-defined sample volumes. The system was shown to be accurate and consistent for blood volumes between 5-15 mu L and for hematocrit levels spanning the range of 25-70%. Finally, a point-of-care DBS sampling device was developed combining the self-powered microfluidic SIMPLE technology. To evaluate the system's practical applicability, a validation study in the context of therapeutic drug monitoring of biologicals was performed using adalimumab-spiked blood samples. Microfluidic DBS samples showed good performance compared to the traditional DBS method with improved recovery rates (86% over 62%). This innovative metering system, allowing for parallelization and integration with complex liquid manipulations, will greatly impact the field of robust sampling, sample preparation, storage and analysis at the point-of-care.

Automated summary

Dried blood spot (DBS) sampling by finger-pricking is gaining attention as an alternative sample collection method. In this work, a novel device and hydrophobic burst valves were developed to address biased analysis data due to variable blood volumes. The innovative metering system showed accurate volume measurement and improved recovery rates, impacting the field of sampling and analysis at the point-of-care.