Point-of-Care Assessment of Hemostasis with a Love-Mode Surface Acoustic Wave Sensor

Abstract

Monitoring of the hemostasis status is essential for therapeutic anticoagulants, undergoing surgery, cardiovascular diseases, etc. Although the clinical values of conventional blood coagulation tests have been well demonstrated, these devices have limitations such as large and expensive equipment, excessive sample volumes, long turnaround times, and difficulty in miniaturization for point-of-care use. Here, we present a novel strategy to evaluate blood hemostasis using the single-port Love-mode surface acoustic wave (SLSAW) sensor. The SLSAW sensor was designed as a plug-and-play-type unit for disposable use and operated under the harmonic resonant mode to produce frequency response to the blood coagulation cascade. Compared with a quartz crystal microbalance, Lamb wave, and film bulk acoustic resonator, the frequency shift of SLSAW was significantly increased, ranging from approximately 8960 to 10 368 kHz, which indicated enhancement of the signal-to-noise ratio. To demonstrate the feasibility of the SLSAW, studies were carried out to examine the effects of temperature and clotting reagents on coagulation times and kinetics. Activated partial thromboplastin times of plasma were validated by comparing with SYSMEX CA-7000 with the correlation (R 2) as 0.996. In terms of coagulation kinetics, reaction time, clot formation time, maximum frequency shift, and clot formation rate of whole blood correlated well with corresponding parameters of the standard thromboelastography (TEG) analyzer (R 2 = 0.9942, 0.9868, 0.9712, and 0.9939, respectively). The SLSAW sensor, with the advantages of low cost, small size, little sample consumption (1 μL), disposable use, and simple operation, is a promising tool for point-of-care diagnosis of hemostasis.

Current Trends on Surface Acoustic Wave Biosensors

“…also engineered a POC device that used a Love mode SAW biosensor to evaluate blood hemostasis. [ 78 ] Their biosensor was designed by lithographic technique on a LiNbO 3 substrate with aluminum IDTs and their results showed a strong positive correlation between their biosensor and other similar commercial products. [ 214–216 ]…”

“…[73] As described by Länge et al, some piezoelectric materials can exhibit high attenuation in liquids because of the dielectric imbalance of the substrate and the liquid, [74] so the DC value of the piezoelectric material remains a key factor in selecting the appropriate substrate. Thus, with regards to the choice of material, lithium niobate (LiNbO 3 ) [46,47,56,[75][76][77][78] and lithium tantalite (LiTaO 3 ) [52,54,[79][80][81][82] have a relatively high DC value and are mostly used as a piezoelectric substrate in many SAW biosensors. Besides of the bulk use, other piezoelectric materials such aluminum nitride (AlN), zinc oxide (ZnO), and lead zirconate titanate (PZT) allow thin film deposition on different substrates including polymers, metallic foils, and plastics.…”

Acoustic Biosensors and Microfluidic Devices in the Decennium: Principles and Applications

“…The SH-SAW sensor has also been demonstrated, with the integration of smartphone technology to develop a low-cost, rapid POC device for the detection of HIV [54]. A disposable, portable unit for monitoring blood hemostasis was demonstrated via the Love mode single port SAW resonator, using an LiNbO 3 substrate [357]. Even though several demonstrations have been made for the successful application of SAW biosensors in the POC devices, the commercialization has not been conducted at a large scale.…”

Point-of-care blood coagulation assay enabled by printed circuit board-based digital microfluidics

“…Microfluidics provides promising tools to develop point-of-care blood assays given its advantages of small size, tiny sample consumption, and versatile prototyping. 9–11 To assess the rheology of blood samples and thus monitor coagulation function, studies using droplet microfluidics, 12 acoustic waves, 13–15 lasers, 16 micropost arrays, 17 mechanical resonance, 18 and electrical impedance 19–21 have been reported. Despite the potential that these methods have shown, the implementation relied on sophisticated instruments such as precision pumps, acoustic transducers, electric measuring instruments, and microscopes, limiting their practical applications.…”