## 2 Sensing Method
### Ultrasonic Sensing
#### 2.4.1 Applied Technologies  
The conversion of acoustic energy into electrical energy via piezoelectric transducers finds the most extensive applications. [PERSON] et al. developed an ultra-tiny \"particle\" sensor integrated with a piezoelectric transducer [80]. This device features a size of less than 0.1 mm and a power consumption of less than 1 nW (Figure 2e). Through the monolithic integration of a customized low-power temperature sensor chip with a micro-piezoelectric transducer fabricated on top of the chip, the miniaturization of the volume was successfully achieved. The device volume is less than 0.1 mm\({}^{3}\), comparable to a grain of table salt. By reducing foreign body rejection and tissue damage, it enhances biocompatibility, enabling it to access narrower interstitial spaces and causing minimal interference to the physiological signals to be measured. Consequently, it can be implanted or injected using minimally invasive techniques with enhanced biocompatibility. This sensor can operate within the temperature range of 25 \({}^{\circ}\)C to 50 \({}^{\circ}\)C, which encompasses all relevant physiological temperatures. The average temperature error from 31 \({}^{\circ}\)C to 35 \({}^{\circ}\)C is approximately 0.044/\(-\)0.040 \({}^{\circ}\)C, and the maximum temperature error across the entire temperature range is approximately \(\pm\)0.2 \({}^{\circ}\)C. In the scenario of multiple sensors implanted simultaneously, the spatial resolution can reach 10 \(\upmu\)m. These data validate its effectiveness as a body temperature sensor. Another application scheme for ultrasound is to utilize the resonant absorption of ultrasound by hydrogels. By design, the volume of the hydrogel can be made sensitive to certain physiological quantities. Corresponding changes in physiological quantities will cause the hydrogel to expand or contract, thereby altering its resonant characteristics. [PERSON] introduced silica nanoparticles into the hydrogel network by loading, which increased the scattering of the propagating ultrasound [81]. The sensor operates in a differential mode, where two sound waves propagate through two different paths; one path contains the hydrogel loaded with silica, and the other path does not. Since the additional attenuation caused by the hydrogel, especially the embedded silica nanoparticles, varies with the volume change in the hydrogel. Therefore, the normalized ratio of the ultrasonic characteristics between the two interfaces is not affected by the changes in tissue characteristics and only depends on the response of the hydrogel to pH, thus making the output independent of the intermediate medium. To maintain the same functional relationship between the swelling behavior of the hydrogel and the pH value, the hydrogel was micropatterned to form a cube shape. A differential pulse echo measurement scheme was used to detect the volume response of the hydrogel. This ultrasonic hydrogel pH sensor successfully measured the pH value at a working distance of approximately 10 cm with a moderate sound intensity (<200 mW/cm\({}^{2}\)). Within the range of the FDA's regulations for imaging ultrasonic intensity (720 mW/cm\({}^{2}\)), using a higher ultrasonic intensity can extend the sensing distance. By replacing the hydrogel loading material, [PERSON] embedded boronic acid groups into the hydrogel, forming a hydrophilic hydrogel network composed of acrylamide, methacrylate, and boronic acid components [82]. This network can produce a reversible volume response to glucose. The hydrogel is designed and shaped to exhibit a mechanical resonance frequency at a specific frequency while remaining acoustically transparent to other frequencies (Figure 2f). Therefore, conventional and continuous ultrasonic imaging can be performed. When tested in mice, during an implantation time of 6 h, the blood glucose was measured uninterruptedly every five minutes using an ultrasonic probe, and the system demonstrated good stability.