Smart MXene‐based bioelectronic devices as wearable health monitor for sensing human physiological signals

Biosafe wearable healthcare monitor has attracted significant attention owing to their applicability to wearable electronics. However, the narrow sensing range and poor response limit the application of flexible devices for comprehensive monitoring of human health‐related physiological signals (i.e., pulse diagnosis). Critical challenges remain in the development of biocompatible materials and the design of flexible bio‐integrated platforms for these purposes, targeting performance approaching those of conventional wafer‐based technologies and long‐term operational stability. In this context, this work presents a robust and flexible MXene/polydopamine (PDA)‐composite‐film‐based pressure sensor in a portable/wearable fashion, which establishes a unique intercalated spherical‐like PDA molecules structure, thereby resulting in excellent sensing performance. The MXene/PDA‐based pressure sensor has sensitivity of up to 138.8 kPa−1 in the pressure range of 0.18–6.20 kPa with fast response and recovery speed (t1 < 100 ms; t2< 50 ms). Associated embodiment involves real‐time precise measurements of a variety of health‐related physiological signals, ranging from wrist pulse, to finger motions, to vocalization and to facial expressions, with high sensitivity and accuracy. Studies on human subjects establish the clinical significance of these devices for future opportunities of health monitoring and intelligent control to predict and diagnose diseases.

opportunities of health monitoring and intelligent control to predict and diagnose diseases.

K E Y W O R D S
MXene, polydopamine, flexible pressure sensors, health monitor INTRODUCTION Recent interest exists in materials and fabrication techniques that enable wearable electronics to be constructed with applications in daily health monitoring, movement tracking, disease diagnosis, and intelligent medicine. [1][2][3][4][5] Such technologies utilize the capability of sensing materials to convert health-related physiological signals into electrical forms of energy. Pressure sensors, to some extent, play a pivotal role in intelligent wearable devices. A significant challenge of conventional pressure sensors exposes the limitations in narrow detection limit, low sensing performance, and unsuitability of large-scale production. Suitable choices of sensing materials, reasonable layout design, and integration fashion have access to establish flexible platforms, in some ways that overcome such limitations. The exertion of sensors formed in compatibility and flexibility could offer opportunities for directly monitoring and long-term stable performance on the soft interfaces.
Effective efforts to the achievement of pressure sensors in high performance involve electronic materials and mechanics principles. For example, carbon materials are highly positive candidates for the construction of pressure sensors, ranging from rigid activated carbon, graphene, carbon black, to carbon nanotubes. [6][7][8] However, the binding forces of these materials must be further improved for practical applications. Additionally, recent works demonstrated that pressure sensors generated by the conversion of textiles or conductive hydrogels usually exhibit excellent performance. In some cases, the sensitivity of micro-pressure monitoring far exceeds the range attainable to the detection, 9 thereby photolithographically manufacturing microstructures (such as pyramids) is more easily achieved than non-structured counterparts. Although the construction of microstructures is intuitively accessible to the enhancement of sensitivity, there are limitations to the production of large areas and the cost of per unit area. 10 The above limitations lead to a better understanding of the selection of pressure-sensitive materials. Previously reported extensive exploration of 2D materials in terms of transition metal carbides, carbonitrides, and nitrides (MXenes) tends to accomplish sophisticated electronic functions. The chemical composition of MXene is M n+1 X n T x , where M, X, and T represent the transition metal, C/N ratio, and surface functional group, respectively, and n represents the number of surface functional groups. 11 The practical possibilities of MXene for the construction of multifunctional devices to advantages in good electrical conductivity, photothermal conversion ability, rich surface chemical properties, and large specific surface area are promising. By comparison with conventional two-dimensional materials (such as graphene oxide), MXene also shows better antibacterial properties, especially in terms of gram-positive and gram-negative bacteria. 12,13 However, because of the low length-to-width ratio, directly assembling MXene nanosheets into the desired macrostructure with the ability of monitoring in real time is difficult, thus limiting their applications. 14 Therefore, MXene displays excellent electrical and mechanical properties, and can be formed in the formats of large areas, the suitable utility of flexible bio-integrated platforms.
Previous studies have confirmed that composites of polymers and MXene have the potential for flexible sensing owing to good processability and low cost. In such systems, polymers such as polyvinyl alcohol, polyvinyl butyral, polydimethylsiloxane, polyvinylidene fluoride, and polyaniline serve as the monomer with MXene for diverse functional composites. [15][16][17][18][19][20] Dopamine (DA) is a natural, non-toxic biomolecule that mimics the structure of the adhesion proteins in mussels and seaweed. It has a large number of amine and catechol functional groups, which are environmentally friendly and can reduce the health risks when applied to human skin, making it very attractive for flexible electronic products. 21 DA adhesively polymerized on the target substrate in situ is well configured for the protection of the circuit. In addition, DA polymerized into polydopamine (PDA) leads to the spontaneous formation of hydrogen bonds with abundant active functional groups. 22 Therefore, the construction of a three-dimensional (3D) MXene/PDA composite film is expected to provide flexible pressure sensors with excellent sensitivity and biosafety.
Here, we report a portable and wearable MXene/ PDA-composite-film-based pressure sensor, in which the key functional constituent consists of the molecular structure of intercalated spherical PDA, thereby contributing to the large-area fabrication technique and the high-performance operation. Systematic studies of formulations of composite films with or without polymerization necessitate the layout design and integration fashion. The sensitivity of the MXene/PDA-based pressure sensor is up to 138.8 kPa −1 when the pressure range is 0.18-6.20 kPa with fast response and recovery speed (t 1 < 100 ms; t 2 < 50 ms). The sensor enables sensitive and accurate modes of precise measurements of various health-related physiological signals in real-time, involving wrist pulse, finger motions, vocalization, and facial expressions. The results demonstrate that MXene/PDA-composite-filmbased pressure sensor serve as the basis of portable and wearable platforms relevant to health monitoring and prediction of disease diagnosis. Figure 1A illustrates the fabrication process for the MXene/PDA composite film. First, MXene (Ti 3 C 2 T x ) nanosheets are prepared by selectively etching an Al layer in the Ti 3 Al 2 C 2 MAX phase. A large number of surface functional groups, such as -O, -OH, and -F, can be generated on the MXene nanosheets, as demonstrated through Raman characterization ( Figure S1). 23,24 Subsequently, DA molecules are adsorbed and further polymerized in situ into the PDA macromolecules on the MXene nanosheets. PDA can be used as a bridge between the MXene sheets to form a unique 3D cross-linked structure. In addition, the hydrogen bond between MXene nanosheets and PDA molecules facilitates the formation of the organicinorganic hybrid membrane after vacuum filtration. The MXene nanosheets are stacked in a lamellar stacking structure after vacuum filtration ( Figure 1B). The fabrication of the pressure sensor is illustrated in Figure 1C.

RESULTS AND DISCUSSION
The MXene/PDA composite membrane is designed as a sandwich structure by covering both sides with flexible Cu electrodes. The flexible film is further encapsulated in polyvinyl chloride (PVC) films for continuous detection. The pressure sensor can be integrated with intelligent devices for commercial medical applications such as monitoring and analyzing the heartbeats and pulse, movements, and subtle signals, including those of sound and swallowing ( Figure 1D), to achieve early warning of physical abnormalities. In Figure 2A, the cross-section image of MXene/PDA composite film shows an ordered layered structure with many interlayer gaps, and the PDA molecules are embedded between the interlaced MXene nanosheets. The top-view scanning electron microscope (SEM) image in Figure 2B indicates that the MXene/PDA film surface was uniform and dense with the PDA molecules. Pristine MXene films are also shown for comparison ( Figure  S2A,B). The atomic force microscopy images further confirmed the rough surface morphology and change in thickness after DA polymerization ( Figure S2C). Transmission electron microscopy (TEM) is used to clarify the morphology and composition of the MXene/PDA composites. As shown in Figure 2C, both the lamellar structure of MXene and the amorphous structure of PDA can be observed in the TEM image, showing that PDA was uniformly distributed on the surface of MXene. The X-ray diffraction (XRD) patterns of MXene/PDA films of different ratios are shown in Figure 2D. The diffraction peak at 2θ = 6.4 • is attributed to the (0 0 2) plane of the MXene nanosheets. Compared with the XRD pattern of the Ti 3 Al 2 C 2 MAX phase ( Figure S3), there is no characteristic peak at 2θ = 39 • , indicating that the product obtained by etching has no impurity-phase Al. To prove the successful compounding of PDA and MXene, the (0 0 2) peaks of the original Ti 3 C 2 T x MXene and composite films are further compared. After polymerization, the blueshifted (0 0 2) diffraction peaks indicate an increase in the nanosheet spacing. The increased layer spacing clearly evidences that the PDA is inserted between the Ti 3 C 2 T x MXene nanosheets. 25 With increase in the DA content, the (0 0 2) diffraction peak increases, however, the (0 0 2) peak shows redshifted with further improvement in the ratio of 1:3. Furthermore, the composite film becomes fragile and it is no longer suitable for flexible monitoring of physical activities. The structures of the MXene, PDA, and MXene/PDA composites are studied by Raman spectroscopy in Figure S1, the Raman peaks at 204, 390, and 627 cm −1 corresponded to the active groups such as -O (A1g of Ti 3 C 2 O 2 ), -F (E g of Ti 3 C 2 F 2 ), and -OH (E g of Ti 3 C 2 (OH) 2 ), 26 respectively. The Raman peak at 1585 cm −1 is assigned to C ═ C stretching benzenoid ring. The Raman peaks of the PDA molecular at 1338, 1415, and 1565 cm −1 are ascribed to C ═ O catechol stretching vibrations. 21 The characteristic Raman peaks for both MXene and PDA prove that the MXene/PDA composite have been successfully prepared. The fourier transform IR (FTIR) spectra of MXene and MXene/PDA composite film are shown in Figure 2E. For MXene, a prominent absorption band at 3452 cm −1 is observed, which could be attributed to the stretching vibration of -OH. 15 The strong absorption band at 3431 cm −1 assigns to the strong hydrogen bonding interaction between MXene and PDA molecules in the composite film. 22,25 The chemical states of MXene and MXene/PDA composite are characterized by XPS. As shown in Figure S4, the XPS survey spectrum indicates that the MXene nanosheets are mainly composed of Ti, C, O, and F elements. 27,28 No related peaks of Al element are detected, indicating that the Al layer has been completely removed during the etching process. 29 The peak intensity of the MXene/PDA composite corresponding to F element is weaker than that of MXene, which could be attributed to the change of the surface after compounding dopamine ( Figure 2F). 30 On the other hand, the introduction of dopamine increases the content of N, O, and C elements. The fine chemical state of MXene and MXene/PDA is further studied. As shown in Figure 2F, it shows the high-resolution Ti 2p spectra of MXene/PDA composite film, which spectrum could be deconvoluted into four peaks at 461.3, 457.1, 455.9, and 455.0 eV, which corresponded to Ti-C 2p 1/2 , Ti 3+ , Ti 2+ , and Ti-C 2p 3/2 , respectively. 22,31 The C 1s spectrum for the MXene/PDA flexible film can be divided into three peaks centered at 286.2, 284.8, and 281.9 eV, and correspond to the presence of C-O/C-N, C-C, and C-Ti bonds, respectively. 32 The Ti-C peak could be attributed to the Ti element in the Ti 3 C 2 T x nanosheets, which is a special feature of the MXene. The C-N bond comes from the PDA. The high-resolution O 1s spectrum of MXene/PDA contains three specific peaks at 532.3, 531.0, and 529.7 eV, which are attributed to C-O, C-Ti-(OH) x , and Ti-O bonds, respectively. 31 Compared with the O 1s spectrum of MXene in Figure S4C, the ratio of Ti-O is determined by 41.9% in MXene, however, it approaches to 22.9% in MXene/PDA composites. The strong reduction of dopamine molecules would inhibit the oxidizable nature of MXene. The specific peak at 685.2 eV is attributed to the F-Ti bonds. The absence of F-Al peak indicates the successful removal of Al element in Ti 3 C 2 T x . 31,33 The influence of dopamine on the sensing behavior is studied at a pressure of 0.93 kPa by adjusting the mass ratios of the MXene nanosheets and dopamine to 1:0, 3:1, 1:1, and 1:3, as shown in Figure S5. The pressure response increases with the increase in the ratio of MXene to DA (1:0, 3:1, 1:1). With an increase in the DA content, the interlayer spacing gradually increases, which produces high deformation and high response under loading pressure. As the ratio of DA is increased further (1:3), the corresponding response decreases under the loading pressure. The above results can be attributed to the following rea-sons: (i) regulation of the conductive path from PDA to MXene nanosheets. Polymers are typically weak conductors of electricity. After combined with PDA, the increased number of conductive paths of the MXene nanosheets results in lower initial current. The interlamellar spacing of the MXene nanosheets decrease with increasing in applied pressure. As shown in Figure 3A and 3B, dopamine molecules are embedded in the MXene nanosheets, which increase the distance between them; this is consistent with the XRD pattern analysis. The increased contact area and conductive paths between the MXene flakes help improve the current conduction of the composite membrane after the application of pressure. (ii) The unique spherical-like structure of PDA provides good deformation performance. The DA molecules are polymerized on the surface of the MXene nanosheets, and a porous structure is fabricated. These porous networks extending into the soft substrate can adjust the compressive deformation distribution in the MXene/PDA hybrid film. Thus, such a layered porous network structure can induce good pressure-sensitive property in flexible sensors. The I-V curves of the flexible pressure sensor with the ratio of MXene to dopamine of 1:1 are obtained at different voltages under different applied pressures. As shown in Figure 3C, the current signal increases with the increasing of the voltage, and the slope of the I-V curves is positively correlated with the exerted pressure, indicating a stable sensitive performance. The dynamic sensitivity curve of the MXene/PDA-based flexible sensor is obtained under different pressure gradients. The sensitivity S is defined as S = δ(ΔI/I 0 )/δ P , where ΔI is the difference between the current after the load pressure and the initial current, I 0 is the initial current, and P is the pressure applied on the sensor. 25 As shown in Figure 3D, the sensitivity of the device gradually increases in the range of 0.18-6.20 kPa, because the soft PDA is easily affected by pressure and the current changes greatly, both high and low pressure forces will cause large deformation of the layered structure of MXene, so as to obtain high sensitivity, so each dynamic response curve is uninterrupted and stable. In Figure 3E, one, two, and five drops of water are used respectively to test the response of the device to the pressure signal. In the low-pressure range, PDA is susceptible to low pressure due to its spherical structure, and the current varies greatly. Therefore, even if a small force is applied, the composite membrane will cause large deformation, resulting in higher sensitivity. This shows that the sensor can clearly distinguish the weight of different droplets, which means it can respond to very small pressure signals. As shown in Figure 3F, the MXene/PDAbased flexible sensor exhibits fast response/recovery speeds of 100 and 50 ms, respectively. Because the spherical structure of PDA has good deformation performance, PDA is easy to be affected by external pressure, the current  16,[34][35][36][37][38][39][40][41] changes greatly, and when the external force is withdrawn, the process of PDA deformation recovery is very fast, so the pressure will cause the rapid deformation of the composite membrane. The fast response and recovery capabilities ensure timely and flexible sensing under the action of external forces. The relationship between sensitivity and applied pressure in Figure 3G can be divided into two areas: (i) in the low-pressure (0.18-2.90 kPa) range, the sensitivity of S 1 was 24.7 kPa −1 ; (ii) in high-pressure (2.90-6.20 kPa) range, the sensitivity of S 2 was 138.8 kPa −1 ( Figure S6).
As displayed in Figure 4A, the MXene/PDA flexible pressure sensor with the flexibility and biocompatibility can be integrated with intelligent system for health monitor, owing to its high sensitivity over a wide sensing range, which can be used for health warning, physiological monitor, diagnose disease and telemedicine ranging from small physiological signals to the human posture. Figure 4B shows the MXene/PDA-based composite thinfilm flexible pressure sensor attached to the curved skin of the index finger joint to stably record the real-time signal changes caused by different finger motions of varying amplitudes, thereby distinguishing between the different bending angles of the fingers (from 30 • to 90 • ). The pulse of the human wrist has clinical significance for indicating the changes in the heart rate and arterial conditions. Therefore, the pressure sensors to detect the pulse on a person's wrist has an immense value. As shown in Figure 4C, the MXene/PDA flexible pressure sensor can be attached to the human wrist to accurately detect the pulse and diagnose potential diseases. The enlarged waveform of the heartbeat with two distinguishable characteristic peaks is displayed, which can be ascribed to the systolic (P 1 ) and diastolic peaks (P 2 ). 35 These results further confirm that the MXene/PDA flexible sensor has excellent sensitivity even when detecting small strains. When different words are spoken, the strain sensor shows different characteristic peaks, that is, different syllables are reflected as changes in the sensor current. The words "flexible" and "carbon" may have complex throat movements, which generate different peak-shaped patterns and differences in insensitivity in Figure 4D. Excellent voice recognition capabilities make the sensor very promising for voice recovery exercises and human-computer interactions. It holds great promise in helping speech-impaired people convey information by recognizing vocal signals. In addition, this flexible sen-sor can recognize subtle changes in the facial expression. For example, when the eyebrows are raised, there was an obvious response with a △I/I 0 value of approximately 12 ( Figure 4E). Furthermore, it can sensitively identify the bending of devices at different angles, the bending angles of 30 • , 45 • , 60 • , and 90 • generate obvious current signal changes, where the bending angle is positively correlated with the sensitivity ( Figure S9). Furthermore, a touch switch system is assembled to realize light adjustment using pressure, which has potential applications in intelligent control. A circuit diagram of the MXene/PDAbased pressure sensor is shown in Figure 4F. The light emitting diode (LED) is dark in the absence of external pressure but lighted up faintly after placing a small screw. The brightness of the LED light gradually increases with the increasing of the applied pressure, indicating the decrease in resistance in the flexible device. Moreover, these results further indicate that flexible devices based on MXene/PDA films may have broad prospects for the development of intelligent controllers and switches, which have applications in various intelligent fields, such as human-computer interaction and intelligent control.

CONCLUSION
In conclusion, MXene/PDA film-based flexible pressure sensors with low health risk and high sensitivity are successfully prepared via dopamine intercalation polymerization. The PDA molecules embedded in MXene nanosheets not only increases the layer spacing of MXene but also acts as a linker to form a 3D cross-linked structure, effectively improving the mechanical and pressure-sensing performance of the device. The sensor has excellent sensitivity (S 1 = 24.7 kPa −1 ; S 2 = 138.8 kPa −1 ) and a relatively short response/recovery time (<100 ms/<50 ms). Flexible pressure sensors can be safely applied to human skin to collect various human vital signs, including biological signs that show tiny deformations, for example, finger bending, pulse, facial expressions, and vocalization. This demonstrates the immense potential of MXene/PDA-based sensing materials for artificial skin and wearable devices.

Synthesis of MXene nanosheets
To synthesize Ti 3 C 2 T x nanosheets from the Ti 3 AlC 2 MAX phase, the etching solution is LiF/HCl. First, a certain amount of LiF and HCl (9 M) was stirred for 30 min to ensure that LiF is dissolved. Then, the solution was heated to 35 • C and the precursor MAX phase was slowly etched at a certain speed for 24 h to etch the Al layer. The resulting solution was repeatedly washed with deionized water until the pH value was higher than 6 to obtain a few layers of Ti 3 C 2 T x nanosheets.

MXene/PDA biocomposite film preparation
First of all, the concentration of the MXene solution was calculated by vacuum filtration. Subsequently, dopamine of different masses was used to control the mass ratios to 1:0; 1:1/3; 1:1, and 1:3. We stirred the solution magnetically for 30 min at a certain speed, then adjusted the pH of the solution to about 8.5, and continued to stir continuously for 12 h under certain conditions. Subsequently, the solvent was removed and a composite membrane was formed by vacuum filtration using a cellulose acetate membrane as a substrate. At last, it was named as MXene/PDA film and dried overnight at room temperature.

Fabrication of flexible pressure sensor
Copper films were first drawn from both ends of the MXene/PDA flexible film as electrodes, and then the two flexible PVC films were cleaned with deionized water, ethanol and acetone, respectively, and covered at both ends of the pressure-sensitive material to prevent material contamination and ensured the stability of the equipment during the test.

Characterization
The crystalline structures of MXene film and MXene/PDA were characterized by XRD (D8-Advance, Germany) with 2θ in the ranges of 5 • -60 • at room temperature. The morphology of the Ti 3 C 2 T x MXene film and MXene/PDA biocomposite film were observed with field emission scanning electron microscopy (FE-SEM, JEOL JSM-7001F, Japan) and TEM (Tecnai G220S-Twin, USA). The thickness and surface topography of sensitive materials were characterized by atomic force microscopy (AFM, Cypher, USA). The surface compositions and chemical states were examined by X-ray photoelectron spectroscopy (XPS, VG ESCALAB 210, USA). The sensing performances are measured by the flexible device analysis system (AES-4SD, SINO AGGTECH, China). Brain-Inspired Technology and the young scientist project of MOE innovation platform.

C O N F L I C T O F I N T E R E S T S TAT E M E N T
The authors declare no conflicts of interest.