# Surface Acoustic Wave Sensor for C-Reactive Protein Detection
## 1 Introduction  
C-reactive protein (CRP) is routinely used as a biomarker to detect inflammation and to assess the future risk of cardiovascular diseases [1, 2]. C-reactive protein is produced in the liver and binds to phosphocholine in damaged or pathogenic cell membranes, inducing an innate immune system response [3]. C-reactive protein concentration in normal human serum is less than 1 \(\mu\)g/mL, but it increases by hundreds of times due to infection and other acute conditions. However, different CRP concentrations generate different response variations. It has been used as a blood test to assess the health of the human body and shows significantly increased serum CRP levels at the site of inflammation [4]. Autoimmune infections, autoimmune diseases, or cancer could be responsible for this. In clinical practice, commonly used CRP detection techniques are radial immunodifusion (RID), radioimmunoassay (RIA), immune repellometry (IN), immune turbidimetry (IT), immunofluorescence, chemiluminescence immunoassay, and standard enzyme immunoassay such as enzyme-linked immunosorbent assays (ELISA) [5, 6]. A fluorescence-linked immunosorbent assay (FLISA) approach was developed after ELISA to reduce the analysis time, because ELISA does not require the chromogenic reaction steps of ELISA [7, 8]. Although these methods are well established with good reproducibility and sufficient sensitivity, they are time-consuming and expensive, which are seen as major limitations. To overcome these limitations, various biosensors for CRP detection analysis based on electrochemical and optical methods [9; 10; 11], surface plasmon resonance (SPR) [12; 13; 14], piezoelectric microcantilevers [15], and quartz crystal microbalance technology [16; 17] have been reported. [PERSON] et al. [18] reported different types of sensors and biosensors for monitoring the concentration of CRP for cardiovascular applications, and some of these biosensors were also suitable for monitoring the wound status. These CRP biosensors were classified as field effect transistors; optical immune-sensors based on surface plasmon resonance; electrochemical sensors based on potentiometry, amperometry, and electrochemical impedance; and piezoresistive sensors, such as quartz crystal microbalances and microcantilevers. According to this report, CRP concentration was less than 8 ug/mL for the normal clinical condition, while higher values (with average CRP level ranging from 20 to 95.6 ug/mL) were used to distinguish between different critical conditions. However, only a few sensors had a wide range (up 35 to 100 ug/mL or 200 ug/mL) that allowed the full spectrum of wound status to be covered. In addition, [PERSON] et al. [19] reported that many biomarkers (e.g., creatinine, CRP, interleukin-6, B-type natriuretic peptide, N-terminal pro B-type natriuretic peptide) may be used as forecasters of cardiac patients' status post cardiac surgery. However, large variations have been observed within these biomarkers. [PERSON] et al. [20] reported that a high level of CRP is not only associated with the presence of atrial fibrillation but may also predict patients at increased risk for future development of atrial fibrillation. The median CRP value of 1.92 ug/mL (interquartile range of 0.97-3.41) was measured based on 897 developed postoperative atrial fibrillation patients. The patients with a higher value of CRP had higher adverse event risk. In this paper, we report the application of a surface acoustic wave (SAW) sensor for CRP detection of up to 1 mg/mL concentration. In recent years, SAW components have been widely used in filters, resonators, mobile phones, television, satellite communications, electronic actuators, sensors, chemical analysis, etc. [21; 22; 23; 24; 25; 26]. Acoustic wave probes based on horizontally polarized shear waves (HPSWs) have been found to be more suitable than vertically polarized shear waves for sensing application in liquids [27]. Love-wave immune-sensors were successfully used for bio-sensing on AT-cut quartz substrates supported by HPSWs [28].