Ultrahigh Sensitive Detection of Tau Protein as Alzheimer's Biomarker via Microfluidics and Nanofunctionalized Optical Fiber Sensors

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative illnesses displaying the highest death rate in the elderly. However, the existing AD diagnostic system remains elusive due to lack of a technology that may ensure enough sensitivity and reproducibility, detection accuracy, and specificity. Herein, a straightforward approach is reported to realize lab‐on‐fiber (LoF) technology for AD biomarker detection based on a D‐shaped single‐mode fiber combined with nanometer‐scale metal‐oxide film. The proposed sensing system, which permits the generation of lossy‐mode resonance (LMR), remarkably increases the evanescent field of light guided through the fiber, and hence the fiber‐surrounding medium interaction. Moreover, such optical sensors are highly repeatable in results and can safely be embedded into a compact and stable microfluidic system. Herein, the specific detection of Tau protein (as one of the classical AD biomarkers that is highly correlated with AD progression) in a complex biofluid with a detection limit of 10−12 m and over a wide concentration range (10−3–10 μg mL−1) is successfully demonstrated. The proposed LoF biosensor is an appealing solution for rapid, sub‐microliter dose and highly sensitive detection of analytes at low concentrations, hereby having the potential toward early screening and personalized medicine in AD.

Analytical Solutions to Fundamental Questions for Lossy Mode Resonance

“…In fact, as for the “decay rate of mode field intensity in surroundings,” it has a more common description “the penetration depth of evanescent wave (EW).” Recently, an ultrahigh sensitive LMR‐based biomarker sensor is proposed. [ 51 ] Owing to the high refractive index of SnO 2 and the D‐shaped SMF, the evanescent field is effectively enlarged and its penetration depth is also enhanced. Then, the sensitivity has been greatly improved and the LOD of biomarker can be lower than 10 −12 M. $$$$\begin{equation}I\left( z \right) = \int_{{d_2}}^{{d_2} + z} {{{\left| {{E_x}\left( {z^{\prime} - {d_2}} \right)} \right|}^2}dz^{\prime}} \end{equation}$$$$To comprehensively consider the interfacial field intensity and decay rate, the mode field integral I ( z ) is calculated shown as Equation (), and the result is given in Figure 4c.…”

“…Recently, an ultrahigh sensitive LMR-based biomarker sensor is proposed. [51] Owing to the high refractive index of SnO 2 and the D-shaped SMF, the evanescent field is effectively enlarged and its penetration depth is also enhanced. Then, the sensitivity has been greatly improved and the LOD of biomarker can be lower than 10 −12 M.…”

Terahertz Plasmonic Sensor Based on Metal–Insulator Composite Woven-Wire Mesh

“…It also modifies the intrinsic properties of analytes [ 2 , 3 ]. In contrast, spectroscopy using electromagnetic waves via free space and integrated solid-state configurations, such as dielectric fibers [ 6 , 7 , 8 ] or slab waveguides, is fast and label-free, but exact light sources from X-rays to microwaves should be selected to achieve noninvasive and nondestructive molecular sensing.…”

Design and fabrication of novel optical fiber architectures for sensing applications

“…One of the most common applications in the case of LMR-based sensors has been the development of refractometers [17,18,39,40]. Nevertheless, there are also other applications including gas detection [41][42][43][44][45], humidity sensors [46][47][48][49], pH sensors [50][51][52], or biosensors [53][54][55][56][57][58].…”

“…2.4b; whereas in [54] the same structure was employed for detecting the D-dimer, a biomarker for venous thromboembolism (VTE), obtaining a LOD of 100 ng/mL, five times below the clinical cutoff value. Other biomolecules that have been detected by means of LMRs include the Tau Protein (an Alzherimer's biomarker) [55] and perfluorooctanoic acid [56].…”