Abstract
D-dimer is a useful diagnostic biomarker for deep vein thrombosis or pulmonary embolism, collectively referred to as venous thromboembolism (VTE). The ability to detect in real-time the amount of D-dimer with a fast and reliable method is a key step to anticipate the appearance of these diseases. Here, the results of a highly specific and sensitive biosensor for the detection of D-dimer based on lossy mode resonance in fiber optics are presented. The unique features of specialty fibers in light management integrated with microfluidics allow detecting D-dimer in human serum with a detection limit of 100 ng/mL, a value 5-fold below the clinical cutoff value. Comparison of the results achieved with mass-spectrometry-based proteomics, which allows for the identification of beta- and gamma-chains of fibrinogen, demonstrates the ability of our platform to specifically (>90%) recognize D-dimer. Therefore, this technology potentially represents a paradigm shift in the development of a simple, high-specificity and label-free biosensing platform, which can be applied to speed up diagnostic healthcare processes of venous thromboembolism toward an early diagnostic and personalized treatment system.
Highlights
D-dimer antigen, the smallest product originated from cross-linked fibrin degradation, is used, above a cutoff value, as a biomarker for deep vein thrombosis or pulmonary embolism, collectively referred to as venous thromboembolism (VTE) (Adam et al, 2009; Kogan et al, 2016)
We describe a simple, high-specificity and label-free lossy mode resonance (LMR)-based biosensing platform consisting of a nanocoated Dshaped fiber for the real-time monitoring of D-dimer, which is a key advance towards theranostic treatments of VTE for personalized medicine
The operation principle consists of monitoring in real time the interaction between a protein (D-dimer) and the specific antibody - the so-called capture antibody grafted on the D-shaped fiber, which induces changes in the thickness of the coating and in the effective refractive index (RI) of the sensing layer
Summary
D-dimer antigen, the smallest product originated from cross-linked fibrin degradation, is used, above a cutoff value, as a biomarker for deep vein thrombosis or pulmonary embolism, collectively referred to as venous thromboembolism (VTE) (Adam et al, 2009; Kogan et al, 2016). The clinical cutoff value of D-dimer is 0.5 μg/mL (manufacturer's recommended threshold for STA®-Liatest® D-di; Stago, Asnières sur Seine Cedex, France) (Linkins and Takach Lapner, 2017; Marill, 2008; Weitz et al, 2017). The best platform for communications and light management, is a good candidate to address the challenge and, at the same time, features unique peculiarities such as small size, lightweight, immunity to electromagnetic interferences and utilization in harsh environments It is sometimes discarded in biosensing because of its low sensitivity. Since the sensitivity to refractive index (RI) is often used as a test for the prediction of the device performance, these values indicate the potential of this type of devices when used as a biosensor Based on this approach, it has been possible to detect immunoglobulin G at femtomolar concentration in human serum (Chiavaioli et al, 2018). Comparison of the results achieved with mass-spectrometry-based proteomics, which was used to prove the grafting of D-dimer to the fiber surface through peptide sequencing and bioinformatics protein identification, demonstrates the ability of the proposed platform to (>90%) recognize D-dimer in diluted and undiluted biological matrices and its reliability
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