Design and evaluation of a portable optical-based biosensor for testing whole blood prothrombin time

Point-of-care diagnostics (POCD) for blood coagulation benefit patients on-site, but available POCD devices are too expensive to be affordable in many countries. Optically based methodologies are cheap and reliable, and have been exploited in bench-top coagulometers to monitor coagulation with plasma, but not whole blood, which contains cellular components that cause massive interference. However, the POCD testing of whole blood gives a more accurate picture of physiological conditions than does testing plasma. In this study, a portable device for performing the prothrombin time (PT) test was designed, comprising an optical sensor, an electrical processing and control circuit to monitor the optical changes that occurred during the coagulation process in whole blood. The PT was when the slope of the first-order derivative of the coagulation curve, recorded from real-time light transmittance signals, was maximal. The POCD PT testing of 167 samples revealed that 153 (91.6%) were successfully detected and the results were highly consistent with the results of whole blood international normalized ratio (INR) (r=0.985, p<0.001) by the conventional manual method and those of plasma INR (r=0.948, p<0.001) with the ACL TOP 700 bench-top coagulometer (Beckman Colter). Hematological parameters were further analyzed, revealing that fibrinogen titers (p=0.036), red blood cell numbers (p=0.017) and distribution of red cell width (p=0.015) affected the effectiveness of the current POCD PT determination. Furthermore, a highly positive correlation was revealed between fibrinogen titers and the maximum speed of change in transmittance (v/t) (r=0.805, p<0.001), suggesting that fibrinogen might be evaluated simultaneously in this POCD testing. In conclusion, the proposed portable optical-based device performs the highly sensitive and accurate determination of whole blood PT and has commercial potential because of its small volume and low fabrication cost.