# Systematic Review on Human Skin-Compatible Wearable Photoplethysmography Sensors
## 3 Photoplethysmography (PPG) Sensor and Its Application
### Applications of PPG Sensor  
In clinical practice, the accurate measurement of the clinically relevant hemoglobin derivatives and bilirubin levels can provide useful diagnostic information. Figure 3 shows the absorption spectra of hemoglobin derivatives and bilirubin that can be further studied using skin-compatible PPG sensors.  
Methemoglobin (MetHb), along with carboxyhemoglobin (COHb) and sulfhemoglobin (SHb), represents a dyshemoglobin that does not bind O\({}_{2}\). Normally, only small traces of MetHb and carboxyhemoglobin (COHb) are found in the blood, while sulfhemoglobin (SHb) is absent [52; 53]. However, levels of MetHb and COHb are often elevated in severely ill patients, including clinical hypoxia [54], exposure to certain toxic agents [55], smokers [56], and the lack of genetic reductase [57].  
Figure 2: **(a)** Illustration of a two-mode (transmission and reflection) PPG sensor. (b) Variation in tissue light attenuation. (c) Molar absorptivity of oxygenated (blue line) and deoxygenated (red line) hemoglobin in arterial blood as of wavelength. Reproduced with permission from [50; 51], ELSEVIER (1997) and SPIE (1999).  
Several observational studies reported the benefits of the continuous monitoring of MetHb and COHb levels to identify patients with carbon monoxide poisoning at triage in the hospital emergency departments [61; 62; 63]. Unlike MetHb, which is reversible with an antidote, methylene blue [64], SHb is an irreversible form of oxidized hemoglobin resulting from the incorporation of a sulfur atom in its porphyrin ring [65; 66]. Currently, devices such as co-oximeters and blood gas analyzers are used to detect the abnormal presence of MetHb and SHb in blood samples [67; 68]. However, the detection tests are not performed routinely in most intensive care units due to cost. The readings provided by those devices are not reliable, giving a false-positive result for methemoglobinemia [69]. Therefore, the noninvasive and low-cost approaches in the detection of MetHb and SHb at the point-of-care would be useful for the early detection of cyanotic conditions. Glyated hemoglobin (HbA1c), which is formed by the binding of hemoglobin, reflects the average blood glucose level over the preceding 60 days [70]. A range of studies [71; 72; 73; 74] have demonstrated the benefits of point-of-care HbA1c testing, and the rapid availability of HbA1c testing has been shown to facilitate safe and effective diabetes management. Bilirubin levels are routinely monitored in cases of neonatal jaundice to identify hyperbilirubin and to prevent bilirubin-related neurotoxicity [75; 76]. Many laboratory devices and methods are available to measure bilirubin levels in the blood. However, results are obtained 24 h after testing leading to delays in treatment. Thus, there is an important need for an accurate point-of-care system that allows rapid and appropriate treatment.  
For the continuous and accurate evaluation of health status, securing stable adhesion between the light-responsive active components of PPG sensors and the target surfaces is crucial by minimizing motion artifacts [77]. Additionally, the devices percutaneously monitoring biometric signals require avoidance of toxicity, electric shock, electrolysis, and excessive thermogenesis [78]. To improve these problems, it is necessary to focus on the development of materials. In the next section, an innovative strategy for human skin-compatible PPG sensors depending on different types of light-absorbing semiconducting materials is highlighted.  
Figure 3: Absorbance of bilirubin and various types of hemoglobin in the visible light region, as mentioned in previous studies. Reproduced with permission from [58; 59; 60], ELSEVIER (1981), SPIE (2012), and ACS Publications (2016).