Flexible Chemical Healthcare Devices
Section 6.2 introduced physical monitoring conditions such as motion, skin temperature, and ECG signals detected from the surface of the skin. These vital signs are important information, but alone are typically insufficient to diagnose health conditions accurately. At a hospital, blood is often taken in combination with checking vital signs. The blood sample checks several things inside the body. However, there is a high probability of causing infection if users self-collect blood samples at home. In addition, the process is inconvenient for real-time monitoring.
A viable alternative may be to detect the chemical contents in sweat or skin gas for real-time continuous monitoring as a wearable device. In fact, sweat or skin gas contains a variety of chemicals, including glucose, potassium, sodium, etc. For example, the glucose level in sweat is correlated with that in the blood (Tierney et al. 2000). Although the absolute value of the glucose level for diagnosis cannot be used, the trend of glucose level changes is more important for wearable healthcare applications. Such trend monitoring is only available for methods using continuous real-time monitoring like a wearable device.
Here, a highly sensitive chemical flexible sensor is introduced. In particular, a pH sensor is discussed because pH detection is a fundamental method for chemical detection using an electrochemical mechanism.
Charge-Coupled Device (CCD)-Based Flexible pH Sensor
Figure 6.9 shows the concept of a pH-monitoring device integrated with a temperature sensor (Nakata et al. 2018). Figure 6.9c shows photos of the device. To prevent direct contact of the solution on the flexible transistors, an extended gate electrode structure was used. For the electrochemical method, the maximum sensitivity is express by Nernst theory as
where Eref is the reference voltage, R is the gas constant, T is the measured temperature, n is the number of electrons transferred, F is the Faraday constant, and is the hydrogen
(a) Schematic, (b) equivalent circuit, and (c) photo of a highly sensitive CCD-based flexible pH sensor. (Reproduced with permission from Nakata et al. (2018). Copyright 2018, Nature Publishing Group.) ion concentration. At room temperature (298 K), the pH sensitivity is limited to ~59 mV/ pH, which is sufficient for pH detection. However, a higher sensitivity may be necessary to precisely and accurately monitor other chemicals like the glucose level in sweat.
To address the theoretically low-sensitivity limitation, the electrically amplified method was proposed using a CCD method, where electrons, which depend on the pH level, are transferred and accumulated in a capacitor. By repeating this process, the sensitivity can be enhanced without increasing the noise level or fabricating a complicated analog circuit. The circuit diagram on a flexible film is shown in Figure 6.9b, and the detailed band diagram to explain the mechanism is described in Figure 6.10a. VICG and VTG work to transfer the electrons injected from V,nput. The number of electrons to transfer is defined by the well depth of the channel between VICG and VTG and corresponds to the pH level (Figure 6.10a(2)). Unlike a conventional Si-based CCD, Vs is also applied to control the Schottky barrier height to efficiently inject electron. It should be noted that the band diagram for Vs is omitted from Figure 6.10a. Schottky junctions are used in this device because
(a) Band diagrams to explain the CCD-based pH sensing mechanism, (b) Output voltage under transfer, accumulation, and reset processes. (Reproduced with permission from Nakata et al. (2018). Copyright 2018, Nature Publishing Group.)
(a) Output voltage at different pH solutions up to 100-cycle transfers and accumulations, (b) Selectivity test conducted by adding sodium and potassium ions over the sensor. (Reproduced with permission from Nakata et al. (2018). Copyright 2018, Nature Publishing Group.)
the formation of a p-n junction is difficult due to limitations of the thermal budget of the doping process for flexible devices.
By turning VICG on, electrons are injected from V,nput to fill the well depth of the pH region (Figure 6.10a(3)). After filling the electron in the well, VICC returns to the off-state (Figure 6.10a(4)). Next, VTG is turned on to extract electrons from the well (Figure 6.10a(5)), which results in charging of all electrons in the integrated capacitor (Figure 6.10a(6)). This accumulation process is repeated to increase the output voltage corresponding to the sensitivity. After reading the output voltage, the reset voltage, VRST, is applied to remove all electrons from the capacitor and to reset the signal.
Figure 6.10b displays the output voltage as a function of accumulation cycles. As described in Figure 6.10a, when VJC is applied, the output voltage negatively increases stepwise. After СК5Т, the output voltage returns to zero, which allows it to continuously measure the pH level in real-time. By changing pH level, the output voltage difference is larger by increasing the transfer and accumulation processes, as described in Figure 6.11a. In this case, after 100 cycles, the pH sensitivity is -240 mV/pH, which is roughly a sensitivity four times higher than the theoretical limit (i.e., 59 mV/pH).
Another important parameter for the chemical sensor is selectivity between different chemicals. Due to the inorganic oxide-based membrane (SiOv) used in this sensor, the sensor only detects the hydrogen ion concentration (i.e., pH level) in a solution. Different chemical solutions (sodium and potassium) with pH 7.1 were also dropped over the sensor (Figure 6.11b). Specifically, 0.1 M sodium and potassium solutions were used. The results clearly indicate that the sensor is only sensitive to the pH level in the solution.
Highly Sensitive Real-Time pH Monitoring
Real-time monitoring of the pH level was conducted by adding different pH solutions into a solution with pH 2.6. Figure 6.12a shows that the CCD-based flexible pH sensor can monitor the pH level continuously. In the experiment, the transfer and accumulation process was repeated 100 times. Each cycle consisted of transfer and accumulation and a
(a) Real-time pH monitoring using the CCD-based pH sensor, (b) Photo and (c) the real-time monitoring of sweat pH and skin temperature detections by attaching sensors onto the skin. (Reproduced with permission from Nakata et al. (20181. Copyright 2018, Nature Publishing Group.)
subsequent reset voltage to reset the accumulation. For a more practical demonstration, the sensor was integrated with a flexible temperature sensor and attached on a human skin with sweat (Figures 6.12b-c). The sensor can monitor the pH level in real human sweat precisely similar to a commercially available stick-type pH meter. In addition, the integrated temperature sensor can monitor the skin temperature and help calibrate the output voltage of the pH sensing. This is because the electrochemical sensors and transistors are temperature dependent, which is critical because the measured temperature is readily changed in wearable applications due to the environmental temperature.