**3. Experiment and Discussion**

#### *3.1. Simulation Results on Static Load*

In this section we use finite element analysis (FEA) to demonstrate that the structure of liquid sealed in a film allows the pressure to be uniformly transmitted to the pressure sensing element, realizing the insensitivity to the stimulus location. The static simulation analysis was performed based on ANSYS. A simulation model for the basic structure of the sensing module was built first, and the same load was applied to different positions on the bulge structure, as shown by the arrows in Figure 6a. The red arrow is the center loading position, and the yellow arrows are the loading positions when the load is offset to the left by 0.5 mm each time (symmetric on the right). The pressure value at the sensing element was calculated separately for each loading position and defined as the output pressure.

The calculated results of the FEA are shown by the red curve in Figure 6b. The *Y*-axis of the curve is the output pressure attenuation relative to the central loading position (red arrow) when loading at other positions (yellow arrows). Results indicate that the output pressure varies with the position of the load, and the attenuation becomes more pronounced away from the center. The output pressure is attenuated by 5.6% at 2.5 mm away from the center and 25% at 4 mm. This means that the output pressure is nearly the same when the stimulus position is within 5 mm of the middle of the sensing module, and the output pressure error is less than 25% within 8 mm. Even at the furthest edge, the sensing module can obtain a valid signal within 30% attenuation. By consideration of adult vessel size, 2.5 mm away from the center is the location that the whole vessel maintains above the sensing bulge; more misplacement leads to the vessel being only partly above the sensing bulge, which results in a larger measuring error. Fortunately, the approximate pulse finger feeling method can easily guarantee that the module is fixed within the ±2.5 mm misplacement tolerance range.

**Figure 6.** Finite element simulation: (**a**) loading positions; (**b**) results of output pressure and film deformation. **Figure 6.** Finite element simulation: (**a**) loading positions; (**b**) results of output pressure and film deformation.

#### *3.2. Location Robustness on Dynamic Stimulation 3.2. Location Robustness on Dynamic Stimulation*

The location robustness in a static load was verified in the simulation analysis. However, the effects of pulse oscillation and epidermal tissue elasticity on pressure signal were not considered in the simulation. Therefore, in this section, the response to the stimulus location of the sensing module under near-real and controlled dynamic conditions is experimentally investigated. The schematic diagram of the experimental platform is shown in Figure 7a. A peristaltic pump was used to simulate the heartbeat, a rubber hose to simulate the blood vessel, and a silica gel pad to simulate the epidermal tissue. The peristaltic pump rollers squeeze the rubber hose from left to right in sequence, intermittently pumping the water through the region where the sensing module is located. The diameter of the rubber hose was 3 mm, which is similar to that of the radial artery vessel. The thickness of the silica gel pad was 5 mm and the hardness was 5 HA, similar to those of the epidermal tissue. The rigid substrate beneath the silica gel pad was used to simulate the radius supporting the radial artery. Figure 7b shows the right elevation of the sensing module and the rubber hose, which illustrates the change in the rubber hose location relative to the sensing module from −5 to 5 mm during the experiment. The photo of the experimental platform is shown in Figure 7c, including a peristaltic pump, a segment of rubber hose, a silica gel pad, a sensing module, a processing circuit, and a smartphone-based recording APP. Figure 7d–f show the close-up photos of the rubber hose positions at the leftmost (−5 mm), middle (0 mm), and rightmost (5 mm), The location robustness in a static load was verified in the simulation analysis. However, the effects of pulse oscillation and epidermal tissue elasticity on pressure signal were not considered in the simulation. Therefore, in this section, the response to the stimulus location of the sensing module under near-real and controlled dynamic conditions is experimentally investigated. The schematic diagram of the experimental platform is shown in Figure 7a. A peristaltic pump was used to simulate the heartbeat, a rubber hose to simulate the blood vessel, and a silica gel pad to simulate the epidermal tissue. The peristaltic pump rollers squeeze the rubber hose from left to right in sequence, intermittently pumping the water through the region where the sensing module is located. The diameter of the rubber hose was 3 mm, which is similar to that of the radial artery vessel. The thickness of the silica gel pad was 5 mm and the hardness was 5 HA, similar to those of the epidermal tissue. The rigid substrate beneath the silica gel pad was used to simulate the radius supporting the radial artery. Figure 7b shows the right elevation of the sensing module and the rubber hose, which illustrates the change in the rubber hose location relative to the sensing module from −5 to 5 mm during the experiment. The photo of the experimental platform is shown in Figure 7c, including a peristaltic pump, a segment of rubber hose, a silica gel pad, a sensing module, a processing circuit, and a smartphone-based recording APP. Figure 7d–f show the close-up photos of the rubber hose positions at the leftmost (−5 mm), middle (0 mm), and rightmost (5 mm), respectively.

The rotational speed of the peristaltic pump is set to 30 rpm and with the three rollers in one circle, i.e., the fluctuation frequency is 90 Hz, which is close to the human heart rate. As each roller passes through the rubber hose, the peak pressure is generated. The signals collected at each location of the sensing module are shown at the bottom of Figure 7g. The top of the figure shows the extracted average oscillating pressure versus its location, and the *Y*-axis is the oscillating pressure attenuation relative to the central

respectively.

**Figure 7.** Experimental setup for location robustness: (**a**) schematic diagram of the experimental platform; (**b**) right elevation of the sensing module; (**c**) photo of the experimental setup; (**d**–**f**) different test locations; (**g**) results of the location robustness experiment. **Figure 7.** Experimental setup for location robustness: (**a**) schematic diagram of the experimental platform; (**b**) right elevation of the sensing module; (**c**) photo of the experimental setup; (**d**–**f**) different test locations; (**g**) results of the location robustness experiment.

*3.3. Individualized Calibration* In this section, the arterial blood pressure (ABP) measured by the sensing module is investigated. The subject's ABP was artificially and quantitatively altered through an in vivo BP control platform to establish a link with the output of the sensing module. This calibration method combines ABP with hydrostatic pressure and is able to assess the effect of individualization factors, such as vessel thickness and epidermal tissue stiffness. The calibration results can be applied to BP tracking for long-term wear. In this study, artificial alteration of ABP was achieved by adjusting the height of the subject's wrist relative to the heart. According to Bernoulli's principle, for every 1.3 cm increase in the height of the wrist relative to the heart, the ABP at the measuring point decreases by 1 mmHg. However, due to the difference in physiological characteristics of the individual body, the signal collected by the sensing module varies from person to person even if the ABP variation is the same. Therefore, it is necessary to recalibrate the sensitivity by the The rotational speed of the peristaltic pump is set to 30 rpm and with the three rollers in one circle, i.e., the fluctuation frequency is 90 Hz, which is close to the human heart rate. As each roller passes through the rubber hose, the peak pressure is generated. The signals collected at each location of the sensing module are shown at the bottom of Figure 7g. The top of the figure shows the extracted average oscillating pressure versus its location, and the *Y*-axis is the oscillating pressure attenuation relative to the central location. As can be seen from the figure, the dynamic experimental results are almost the same as the static simulation results. At a distance of ±4 mm from the center, the oscillating pressure decays by 23.7%. The ideal measuring location is from −2.5 to 2.5 mm and the oscillating pressure variation is within 5.4%. Another important result is that the waveforms maintained a close agreement at all the misalignment locations, which is one of the key performances desired in real BP monitoring. In this manner, the designed sensing module demonstrated its capability of alignment-free tonometry BP measurement.

location. As can be seen from the figure, the dynamic experimental results are almost the same as the static simulation results. At a distance of ±4 mm from the center, the oscillating pressure decays by 23.7%. The ideal measuring location is from −2.5 to 2.5 mm and the oscillating pressure variation is within 5.4%. Another important result is that the waveforms maintained a close agreement at all the misalignment locations, which is one of the key performances desired in real BP monitoring. In this manner, the designed sensing module demonstrated its capability of alignment-free tonometry BP measurement. Based on the developed alignment-free sensing module, it was necessary to examine its appropriate capability in BP measuring, which is presented in the following sections.

controlled ABP and the corresponding sensor output. The experimental setup includes a wrist height adjustment platform, as shown in Figure 8a, which is designed with a sliding track allowing the subjects to maintain the Based on the developed alignment-free sensing module, it was necessary to examine its appropriate capability in BP measuring, which is presented in the following sections.

#### posture while changing the height of the wrist. The subject selected for the experiment *3.3. Individualized Calibration*

was healthy, did not smoke, drink, or exercise before the experiment, and was in a resting In this section, the arterial blood pressure (ABP) measured by the sensing module is investigated. The subject's ABP was artificially and quantitatively altered through an in vivo BP control platform to establish a link with the output of the sensing module. This calibration method combines ABP with hydrostatic pressure and is able to assess the effect of individualization factors, such as vessel thickness and epidermal tissue stiffness. The calibration results can be applied to BP tracking for long-term wear. In this study, artificial alteration of ABP was achieved by adjusting the height of the subject's wrist relative to the heart. According to Bernoulli's principle, for every 1.3 cm increase in the height of the wrist relative to the heart, the ABP at the measuring point decreases by 1 mmHg. However, due to the difference in physiological characteristics of the individual body, the signal collected by the sensing module varies from person to person even if the

in Figure 8b.

ABP variation is the same. Therefore, it is necessary to recalibrate the sensitivity by the controlled ABP and the corresponding sensor output. By the analysis of the experimental data, it can be found that the primary change in the signal as the wrist height rises is the decrease in mean pressure. The change rate is

state without any stimulus during the experiment. Therefore, the BP of the subject was considered to be stable and did not fluctuate significantly during the experiment. The experimental procedure started with finding the height of the heart and defining it as 0 cm. The wrist height was adjusted within ±20 cm, starting from −20 cm and rising 10 cm each time. Each position measurement lasted 30 s, and the measured pulse wave is shown

The experimental setup includes a wrist height adjustment platform, as shown in Figure 8a, which is designed with a sliding track allowing the subjects to maintain the posture while changing the height of the wrist. The subject selected for the experiment was healthy, did not smoke, drink, or exercise before the experiment, and was in a resting state without any stimulus during the experiment. Therefore, the BP of the subject was considered to be stable and did not fluctuate significantly during the experiment. The experimental procedure started with finding the height of the heart and defining it as 0 cm. The wrist height was adjusted within ±20 cm, starting from −20 cm and rising 10 cm each time. Each position measurement lasted 30 s, and the measured pulse wave is shown in Figure 8b. −4.25 mV/cm; that is, the sensitivity of the sensing module is 5.7 mV/mmHg. However, the sensitivity of the sensor was previously calibrated as 8.7 mV/mmHg in a precise pressure chamber. The error between the measured and calibrated sensitivity is a reflection of the individualization factor. This can be explained in two ways. One is that the epidermal tissue induces an attenuation effect on pressure transmission [23,24]. The other is that only part of the sensitive area is in contact with the arterial blood vessels during the measurement, as shown in Figure 5a. The first factor is related to the elasticity and thickness of the epidermis, and the second factor is influenced by the thickness of the artery. Both factors can be attributed to the individualized discrepancies and can be eliminated by recalibration.

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**Figure 8.** Individualized calibration results. (**a**) Experimental setup for ABP control. (**b**) Pulse signals at different heights. (**c**) Recalibrated sensitivity. **Figure 8.** Individualized calibration results. (**a**) Experimental setup for ABP control. (**b**) Pulse signals at different heights. (**c**) Recalibrated sensitivity.

*3.4. BP Calibration* The individualized factor calibration characterizes the relationship between the variation in the sensing module output and BP during ambulatory BP measurements. However, because the wearing state is different each time, the initial BP also needs to be calibrated. The characteristics of the transmural pressure can be used to calibrate the initial BP. The transmural pressure represents the combined pressure of intravascular pressure, applied pressure, and hydrostatic pressure. It is generally accepted that the compliance of By the analysis of the experimental data, it can be found that the primary change in the signal as the wrist height rises is the decrease in mean pressure. The change rate is −4.25 mV/cm; that is, the sensitivity of the sensing module is 5.7 mV/mmHg. However, the sensitivity of the sensor was previously calibrated as 8.7 mV/mmHg in a precise pressure chamber. The error between the measured and calibrated sensitivity is a reflection of the individualization factor. This can be explained in two ways. One is that the epidermal tissue induces an attenuation effect on pressure transmission [23,24]. The other is that only part of the sensitive area is in contact with the arterial blood vessels during the measurement, as shown in Figure 5a. The first factor is related to the elasticity and thickness of the epidermis, and the second factor is influenced by the thickness of the artery. Both factors can be attributed to the individualized discrepancies and can be eliminated by recalibration.

#### *3.4. BP Calibration* the MBP, is equal to the extravascular pressure when the hydrostatic pressure is equal to

The individualized factor calibration characterizes the relationship between the variation in the sensing module output and BP during ambulatory BP measurements. However, because the wearing state is different each time, the initial BP also needs to be calibrated. The characteristics of the transmural pressure can be used to calibrate the initial BP. The transmural pressure represents the combined pressure of intravascular pressure, applied pressure, and hydrostatic pressure. It is generally accepted that the compliance of the vessel increases to a maximum value as the transmural pressure goes to zero [25]. In addition, the transmural pressure equal to zero means that the intravascular pressure, i.e., the MBP, is equal to the extravascular pressure when the hydrostatic pressure is equal to zero. This also means that the pulse oscillating pressure measured by the sensing module is the largest [26]. Furthermore, maximum vascular compliance also means that the same pressure change in the vessel causes the most significant change in vessel volume and, therefore, the most extended PWTT [27]. Thus, there can be two ways to determine the initial BP—when the pulse oscillation amplitude reaches its maximum and when the PWTT is the longest. In this study, the transmural pressure was varied by changing the applied pressure of the sensing module, and was decreased to zero and then increased in reverse as the applied pressure increases. zero. This also means that the pulse oscillating pressure measured by the sensing module is the largest [26]. Furthermore, maximum vascular compliance also means that the same pressure change in the vessel causes the most significant change in vessel volume and, therefore, the most extended PWTT [27]. Thus, there can be two ways to determine the initial BP—when the pulse oscillation amplitude reaches its maximum and when the PWTT is the longest. In this study, the transmural pressure was varied by changing the applied pressure of the sensing module, and was decreased to zero and then increased in reverse as the applied pressure increases. The experimental setup containing a pressure controller, a gasbag, and an ABP measurement device is shown in Figure 9a. The pressure applied to the wrist by the sensing module was controlled by the pressure controller and a gasbag above the module. Before the experiment, the subject was required to align the sensing module with the gasbag after wearing the ABP measurement device, and the subject's wrist remained stationary throughout the experiment. The pressure on the wrist was then controlled to increase gradually and uniformly until the acquired pulse waveform begins to distort, indicating that the artery is almost closed. The experimental results for one subject are presented in Figure 9b. The mean

the vessel increases to a maximum value as the transmural pressure goes to zero [25]. In addition, the transmural pressure equal to zero means that the intravascular pressure, i.e.,

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The experimental setup containing a pressure controller, a gasbag, and an ABP measurement device is shown in Figure 9a. The pressure applied to the wrist by the sensing module was controlled by the pressure controller and a gasbag above the module. Before the experiment, the subject was required to align the sensing module with the gasbag after wearing the ABP measurement device, and the subject's wrist remained stationary throughout the experiment. The pressure on the wrist was then controlled to increase gradually and uniformly until the acquired pulse waveform begins to distort, indicating that the artery is almost closed. pressure measured by the sensing module keeps rising uniformly with the increase in the applied pressure. The oscillating pressure and the PWTT also progressively increase at the beginning due to the decreased transmural pressure. As the applied pressure continued to increase, the oscillating pressure and the PWTT started to decrease from a certain point because the transmural pressure decreased to zero and then increased in reverse. The turning point is the MBP state for the subject, as shown by the dashed line in Figure 8c. The mean pressure at this point corresponds to the MBP, and the oscillating pressure corresponds to the difference between systolic and diastolic pressures.

**Figure 9.** Pulse characteristics at different applied pressures.(**a**) Experimental setup for initial BP calibration. (**b**) Mean pressures and oscillating pressures. (**c**) PWTT. **Figure 9.** Pulse characteristics at different applied pressures.(**a**) Experimental setup for initial BP calibration. (**b**) Mean pressures and oscillating pressures. (**c**) PWTT.

The experimental results for one subject are presented in Figure 9b. The mean pressure measured by the sensing module keeps rising uniformly with the increase in the applied pressure. The oscillating pressure and the PWTT also progressively increase at the beginning due to the decreased transmural pressure. As the applied pressure continued to increase, the oscillating pressure and the PWTT started to decrease from a certain point be-

cause the transmural pressure decreased to zero and then increased in reverse. The turning point is the MBP state for the subject, as shown by the dashed line in Figure 8c. The mean pressure at this point corresponds to the MBP, and the oscillating pressure corresponds to the difference between systolic and diastolic pressures.

According to the IEEE standard [28], twenty healthy adults were selected for evaluating the effectiveness of the designed BP measurement device. Their personal information and BP measured by a commercial sphygmomanometer (Omorn Inc., Japan, HEM-7124) 5 min before the test are shown in Table 1. The initial BP was calibrated by the same method for the 20 subjects, and the extracted mean and oscillating pressures are presented in Figure 10. The calibration results of the MBP are shown in red.

Because the BP procedure in this study is based on arterial tonometry, the MBP was obtained from the corresponding mean pressure, and the differential pressure (DP) between systolic pressure and diastolic pressure was obtained from the corresponding oscillating pressure. The BP measurement results of the subject were determined by the MBP and the DP. In order to enable comparison with the commercial cuff sphygmomanometers, the results were converted to SBP and DBP by the 4/6 principle. Then, the Bland–Altman method was used to analyze the correlation between the derived BP and the BP measured by the commercial sphygmomanometer; the results are shown in Figure 11. All measuring results fall within the confidence interval. The mean error of SBP is −4.62 mmHg with a standard deviation of ±7.0 mmHg, and the mean error of DBP is 2.98 mmHg with a standard deviation of ±5.07 mmHg. The BP measurement results are in accordance with the AAMI standard [29] of 5 ± 8 mmHg. The above experimental results indicate that the BP measurement device proposed in this paper has considerable stability and can adapt to different people.


**Table 1.** BP information for the 20 subjects.

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**Figure 11.** Bland–Altman analysis of (**a**) SBP and (**b**) DBP. **Figure 11.** Bland–Altman analysis of (**a**) SBP and (**b**) DBP. **Figure 11.**Bland–Altman analysis of (**a**) SBP and (**b**) DBP.

#### **4. Conclusions 4. Conclusions 4. Conclusions**

Arterial tonometry is a noninvasive BP measurement method with high accuracy. However, sensor–artery alignment is a major problem that obstructs the application of arterial tonometry. In this study, a novel solid–liquid mixture pulse sensing module was proposed to address the existing problems. The flexible film with semicylindrical bulges and unique liquid-filled structure greatly reduces the pulse measuring error caused by Arterial tonometry is a noninvasive BP measurement method with high accuracy. However, sensor–artery alignment is a major problem that obstructs the application of arterial tonometry. In this study, a novel solid–liquid mixture pulse sensing module was proposed to address the existing problems. The flexible film with semicylindrical bulges and unique liquid-filled structure greatly reduces the pulse measuring error caused by Arterial tonometry is a noninvasive BP measurement method with high accuracy. However, sensor–artery alignment is a major problem that obstructs the application of arterial tonometry. In this study, a novel solid–liquid mixture pulse sensing module was proposed to address the existing problems. The flexible film with semicylindrical bulges and unique liquid-filled structure greatly reduces the pulse measuring error caused by

position deviation. Having a rational circuit and algorithm design, it is able to extract the mean and oscillating pressures of the subject's pulse. In addition, the device has the ability to measure PWTT, which can serve as a complement to arterial tonometry and is especially suitable for ambulatory BP monitoring. The location robustness of the sensing module was verified by simulation and experiment. The ideal measuring location ranges from −2.5 to 2.5 mm of the module and the pressure variation is within 5.4%, which can be easily achieved by finger feeling in a real application of a wearable BP monitoring scenario. At a distance of ±4 mm from the module center, although the pressure decays by 23.7%, the dynamic waveform is conserved well, which is important for wearable application. For different potential users, the individualization factor can be calibrated by an ABP control platform, and the initial BP can be calibrated by an applied pressure regulation platform. The alignment deviation errors can be further eliminated by the individual calibration procedure in a practical BP measuring step. BP measurement experiments were performed on 20 subjects, and the experimental procedure followed IEEE standards. The results indicate that the wearable device performs well for BP measurements and the error of the results meet the AAMI standards. The device is expected to provide a new solution for wearable continuous BP monitoring.

In next phase, we plan to (1) combine arterial tonometry and the PWTT method for BP measurement, and use the device for noninvasive continuous BP measurement in clinical trials; (2) study the interference of human motion on the measurement, and improve the accuracy of the measurement in motion in terms of the device structure design and an anti-motion algorithm.

**Author Contributions:** Conceptualization, W.L.; software, B.Z.; validation, B.Z., C.Y. and F.X.; formal analysis, B.Z.; data curation, C.Y. and F.X.; writing—original draft preparation, B.Z.; writing—review and editing, W.L.; supervision, W.L. and X.F.; funding acquisition, W.L., L.H. and X.F. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research work was financially supported by the National Natural Science Foundation of China, grant number 51875506, the Science Fund for Creative Research Groups of National Natural Science Foundation of China, grant number 51821093, the National Natural Science Foundation of China, grant number 51775485.

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Medical Ethics Committee of College of Biomedical Engineering & Instrument Science, Zhejiang University ([2021]-39).

**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.

**Acknowledgments:** The authors are also sincerely grateful to the students participating in the experiment.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

