Paper-Based Lateral Flow Device for the Sustainable Measurement of Human Plasma Fibrinogen in Low-Resource Settings

Abstract

Fibrinogen concentration is a major determinant of both clotting and bleeding risk. Clotting and bleeding disorders cause extensive morbidity and mortality, particularly in resource-poor and emergency settings. This is exacerbated by a lack of timely intervention informed by measurement of fibrinogen levels under conditions such as thrombosis or postpartum haemorrhage. There is an absence of simple, rapid, low-cost, and sustainable diagnostic devices for fibrinogen measurement that can be deployed in such environments. Paper-based analytical devices are of significant interest due to their potential for low-cost production, ease of use, and environmental sustainability. In this work, a device for measuring blood plasma fibrinogen using chromatography paper was developed. Wax printing was used to create hydrophobic structures to define the test channel and sample application zone. Test strips were modified with bovine thrombin. Plasma samples (22 μL) were applied, and the flow rate was monitored over 5 min. As the sample traversed the strip, clotting was induced by the conversion of soluble fibrinogen to insoluble fibrin. The flow rate and distance travelled by the sample were dependent on fibrinogen concentration. The device was able to measure fibrinogen concentration in the range of 0.5–7.0 ± 0.3 mg/mL ( p < 0.05, n = 24) and had excellent correlation with laboratory coagulometry in artificial samples ( r 2 = 0.9582, n = 60). Devices were also stable at 4–6 °C for up to 3 weeks.

Toward Next Generation Lateral Flow Assays: Integration of Nanomaterials

“…The device is simple, portable, and cost-effective, enabling the PoC semiquantification of fibrinogen in a range of 0.5 to 7.0 mg mL −1 . 33 The use of rulers has also been reported by Li et al, albeit in a much more complex system. The working principle of their assay relies on the use of antibody-functionalized platinum nanoparticles (PtNPs) that are captured on the TL as in a conventional LFA.…”

“…This enables the visual monitoring of the distance traveled by the sample. The device is simple, portable, and cost-effective, enabling the PoC semiquantification of fibrinogen in a range of 0.5 to 7.0 mg mL –1 . The use of rulers has also been reported by Li et al, albeit in a much more complex system.…”

Development of a paper-based lateral flow prothrombin assay

“…Not unexpectedly, a similar trend has been observed in the development of a paper-based lateral flow fibrinogen assay. 30 Variability due to operational temperature could be addressed through the use of specific temperature calibration ranges.…”

Development of Novel Paper-Based Assay for Direct Serum Separation

“…On the other hand, storing strips at ambient temperature gave acceptable measurements after the first week only, as increased desiccation might increase paper and reagent hydrophobicity. The addition of stabilizers, excipients, and processing techniques such as lyophilization can help store thrombin activity and enhance storage efficacy . The assay used by Hegener et al was stored in controlled room temperature of 20–22 °C and was used successfully within 3 months of production …”

“…Multiple recent reviews have highlighted the promising value of paper-based, microfluidic, and lab-on-a-chip technologies for POC diagnosis and monitoring of hemostasis and coagulation. − Many paper-based devices were developed to assess whole blood coagulation, , plasma fibrinogen concentration, ,− detection of thrombin, and anticoagulation therapy monitoring. , A microfluidic sensor named “ClotChip” was developed for POC assessment of hemostasis. , Another microfluidic chip coated with PT reagent was developed for blood coagulation assessment . A microfluidic paper analytic POC device was used for monitoring of direct thrombin inhibitors .…”