Point-of-care coagulation monitoring: first clinical experience using a paper-based lateral flow diagnostic device

Abstract

Vitamin K antagonists such as warfarin are the most widely used class of oral anticoagulants. Due to a narrow therapeutic window, patients on warfarin require regular monitoring. Self-testing using point-of-care (POC) diagnostic devices is available, but cost makes this monitoring method beyond reach for many. The main objective of this research was to assess the clinical utility of a low-cost, paper-based lateral flow POC diagnostic device developed for anticoagulation monitoring without the need for a separate electronic reader. Custom-fabricated lateral flow assay (LFA) test strips comprised of a glass fiber sample pad, a nitrocellulose analytical membrane, a cellulose wicking pad, and a plastic backing card were assembled in a plastic cassette. Healthy volunteers and patients on warfarin therapy were recruited for this prospective study. For each participant, a whole blood sample was collected via fingerstick to determine: (1) international normalized ratio (INR) using the CoaguChek® XS coagulometer, (2) hematocrit by centrifugation, and (3) red blood cell (RBC) travel distance on the experimental LFA device after 240 s using digital image analysis. RBC travel distance measured on the LFA device using blood samples obtained from warfarin patients positively correlated with increasing INR value and the LFA device had the capability to statistically distinguish between healthy volunteer INR values and those for patients groups with INR ≥ 2.6. From these data, it is predicted that this low-cost, paper-based LFA device can have clinical utility for identifying anticoagulated patients taking vitamin K antagonists who are outside of the desired therapeutic efficacy window.

Microfluidics in Haemostasis: A Review

“…The correlation between the distance travelled by RBCs and INR was established and further validated with the results obtained from the commercially available POC CoaguChek ® device. The novel test strip presented a qualitative interpretation of INR results in terms of 'Low,' 'OK,' and 'High' [75]. A different application of a smartphone detection system is schematically represented in Figure 9C.…”

“…Paper contains cellulose as a key component and possesses advantages in terms of its distinct properties, such as being lightweight, inexpensive, readily accessible and can be chemically modified to enhance its biological compatibility for integrating different functional groups to it [94,95]. Recently, a paper-based diagnostic micro-device was developed to study blood viscosity and coagulation time that costs less than 50 cents per device [75]. A unique combination of paper on PDMS, as discussed earlier, was used to develop a microfluidic device for a POC application.…”

“…B. Experimental set-up showing a digital camera mounted over the paper-based microfluidic device to capture images every 15s during the test[75]. C. Smartphone based detection system of a paper-on-polydimethylsiloxane (PDMS) device using LED emission light.…”

“…(A) Charged-coupled device (CCD) optical detection of the laser beam transmitted to the microfluidic device developed for a platelet aggregation study[74]. (B) Experimental set-up showing a digital camera mounted over the paper-based microfluidic device to capture images every 15s during the test[75]. (C) Smartphone based detection system of a paper-on-polydimethylsiloxane (PDMS) device using LED emission light.…”

Microfluidic and Paper-Based Devices for Disease Detection and Diagnostic Research

“…Several disorders exist that can attack the major constituents of blood including red blood cells, white blood cells, and platelets. Clinical detection of blood cells can alert lab technicians to the presence of these diseases by analyzing red blood cells [ 51 , 52 ], white blood cells [ 53 , 54 , 55 ], and platelets [ 56 ]. Several blood diseases affect the structure or function of RBCs including anemias, polycythemias, and hemolysis.…”