TiO2-MXene/PEDOT:PSS Composite as a Novel Electrochemical Sensing Platform for Sensitive Detection of Baicalein

In this work, TiO2-MXene/poly (3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) composite was utilized as an electrode material for the sensitive electrochemical detection of baicalein. The in-situ growth of TiO2 nanoparticles on the surface of MXene nanosheets can effectively prevent their aggregation, thus presenting a significantly large specific surface area and abundant active sites. However, the partial oxidation of MXene after calcination could reduce its conductivity. To address this issue, herein, PEDOT:PSS films were introduced to disperse the TiO2-MXene materials. The uniform and dense films of PEDOT:PSS not only improved the conductivity and dispersion of TiO2-MXene but also enhanced its stability and electrocatalytic activity. With the advantages of a composite material, TiO2-MXene/PEDOT:PSS as an electrode material demonstrated excellent electrochemical sensing ability for baicalein determination, with a wide linear response ranging from 0.007 to 10.0 μM and a lower limit of detection of 2.33 nM. Furthermore, the prepared sensor displayed good repeatability, reproducibility, stability and selectivity, and presented satisfactory results for the determination of baicalein in human urine sample analysis.


Introduction
Baicalein (5,6,7-trihydroxyflavone), as a kind of natural flavonoid isolated from Scutellaria [1], has generally been utilized for the prevention and treatment of physical diseases [2,3]. According to previous reports, baicalein is widely used in anti-cancer, antiinflammatory and anti-viral therapy [4][5][6]. Nevertheless, overdosing baicalein will inevitably result in serious side effects such as spasm, dizziness and coma [7]. Thus, the development of an accurate and sensitive method of detection for baicalein has aroused widespread attention. In this context, electrochemical sensors have attracted broad-scale research because of their high sensitivity, rapid response, simplified operation and low cost [8][9][10]. For an electrochemical sensing platform, selecting suitable electrode materials to promote detection performance it is a critical factor.
As a rapidly growing family of two-dimensional (2D) materials, MXene has gradually become a hot topic of important research in the field of electrochemical sensors [11]. Due to its metallic-like conductive nature, abundant surface groups and superior mechanical properties [12][13][14], MXene possesses excellent electrochemical properties and has been extensively applicated in electrochemical sensors [15]. Among various MXenes, Ti 3 C 2 is the most widely used [16]. However, the strong self-stacking and agglomeration of the Ti 3 C 2 nanosheets can sharply decrease the electrochemical performance [17], which will limit the practical application of the MXene. To overcome these drawbacks, the introduction of nanoparticles to modify the surface of MXene nanosheets is an effective and suitable approach to expanding the interlayer spacing of MXene nanosheets [18]. The edge Ti atom on the surface of Ti 3 C 2 T x as a nucleation site could easy to generate TiO 2 nanoparticles with rich oxygen vacancies (OVs) through the controlled oxidation of Ti 3 C 2 T x [19]. The formed OV-TiO 2 nanoparticles embedded in MXene sheets could effectively broaden the layer spacing. Moreover, the oxygen vacancies are conducive to promoting the formation of new active sites [20], which further boost the chemical adsorption capability. Despite such advantages, the partial oxidation of MXene inevitably decreases electrical conductivity. In addition, oxidation destroys the surface functional groups and reduces the water stability of MXene, which greatly restricts its applications in electrochemical sensing.
PEDOT:PSS is an extensively studied conductive polyelectrolyte complex with the structure of PEDOT-rich cores surrounded by a PSS-rich shell [21]. PEDOT:PSS has been used in the areas of thermoelectricity, organic photovoltaics, bioelectronics and sensing conductors [22][23][24][25] because of its high conductivity, appropriate stability and superior mechanical flexibility [26,27]. In the fabrication of electrochemical sensors, PEDOT:PSS could be used as conductive dispersant to enhance the dispersibility of other materials. Furthermore, the addition of nanomaterials makes it feasible to improve the physicochemical properties of PEDOT:PSS. As a proof of concept, the TiO 2 -MXene/PEDOT:PSS composite can be rationally designed. Until now, there has been no report on the fabrication of TiO 2 -MXene/PEDOT:PSS film as electrochemical sensor for baicalein detection.
In this work, we proposed a novel electrochemical sensing platform for baicalein determination based on a TiO 2 -MXene/PEDOT:PSS-modified glassy carbon electrode (GCE). The TiO 2 -MXene/PEDOT:PSS composite was prepared by oxygen vacancy-rich TiO 2 -MXene followed by direct ultrasonic mixing with PEDOT:PSS. VO-TiO 2 embedded in MXene not only enhanced electron transfer but also possessed a relatively large surface area. The introduction of PEDOT:PSS film can further increase the stability and conductivity of the composite. Benefited by the synergistic effect between TiO 2 -MXene and PEDOT:PSS, the prepared sensor exhibited a wide linear working range and a low limit of detection (LOD) towards baicalein detection. Furthermore, the designed electrochemical sensor showed good selectivity and stability for baicalein detection, and it was also successfully applied to the detection of baicalein in real samples.

Characterization of Structure and Morphology
The morphological characterizations of MXene, TiO 2 -MXene and TiO 2 -MXene/PEDOT:PSS were observed by scanning electron microscopy (SEM). As presented in Figure 1A, the pristine MXene possessed a typical layered accordion-like structure with a smooth surface. For TiO 2 -MXene ( Figure 1B), the surface of MXene became rough, and there were many fine TiO 2 nanoparticles on the surface or inside of the MXene nanosheets. The TiO 2 nanoparticles could effectively hinder the stacking of MXene sheets and extend the interlayer distance, and thus more catalytic active sites were exposed. Simultaneously, the unique layered structure of MXene could be a large platform for loading TiO 2 nanoparticles. After combining with PEDOT:PSS ( Figure 1C), it could be seen that the surface of TiO 2 -MXene became smoother because of the great film-forming property of PEDOT:PSS. Additionally, the coating of PEDOT:PSS on the surface of TiO 2 -MXene did not change the morphology of TiO 2 -MXene.
The X-ray photoelectron spectroscopy (XPS) spectra were utilized to study the elemental composition on the surface of the TiO 2 -MXene composites. As displayed in Figure 2A, the XPS survey spectrum proved the presence of C, Ti, O and F elements in TiO 2 -MXene. In the Ti 2p spectrum ( Figure 2B), the peaks at 453.7, 454.1, 454.6 and 457.3 eV were attributed to Ti-C, Ti-X from Ti (II), Ti ions with reduced charge state (Ti x O y ) and TiO 2 , respectively. The peak of TiO 2 indicated that Ti 3 C 2 T x partly transformed into TiO 2 nanoparticles. Furthermore, the XPS spectrum of C1s ( Figure 2C) exhibited three fitted peaks at 281.3, 284.8 and 286.6 eV, which could be assigned to C-Ti, C-C and C-O, respectively. According to the spectrum of O 1s ( Figure 2D), the binding energies at 529.8, 530.3, 531.2 and 532.5 eV could be ascribed to absorbed O species, Ti-O-Ti, Vo defect and Ti-OH [28]. These results proved the successful preparation of oxygen vacancy-rich TiO 2 -MXene through annealing, which played a role in providing ample active sites and then enhanced the baicalein absorption. The X-ray photoelectron spectroscopy (XPS) spectra were utilized to study the elemental composition on the surface of the TiO2-MXene composites. As displayed in Figure  2A, the XPS survey spectrum proved the presence of C, Ti, O and F elements in TiO2-MXene. In the Ti 2p spectrum ( Figure 2B), the peaks at 453.7, 454.1, 454.6 and 457.3 eV were attributed to Ti-C, Ti-X from Ti (Ⅱ), Ti ions with reduced charge state (TixOy) and TiO2, respectively. The peak of TiO2 indicated that Ti3C2Tx partly transformed into TiO2 nanoparticles. Furthermore, the XPS spectrum of C1s ( Figure 2C) exhibited three fitted peaks at 281.3, 284.8 and 286.6 eV, which could be assigned to C-Ti, C-C and C-O, respectively. According to the spectrum of O 1s ( Figure 2D), the binding energies at 529.8, 530.3, 531.2 and 532.5 eV could be ascribed to absorbed O species, Ti-O-Ti, Vo defect and Ti-OH [28]. These results proved the successful preparation of oxygen vacancy-rich TiO2-MXene through annealing, which played a role in providing ample active sites and then enhanced the baicalein absorption.

Electrochemical Characterizations
The electrochemically active surface area (ECSA) was one of the key factors affecting the performance of electrode materials. The ECSA of the electrode material was estimated by cyclic voltammetry (CV) measurements with different scan rates (10-80 mV·s −1 ) in 5  The X-ray photoelectron spectroscopy (XPS) spectra were utilized to study the elemental composition on the surface of the TiO2-MXene composites. As displayed in Figure  2A, the XPS survey spectrum proved the presence of C, Ti, O and F elements in TiO2-MXene. In the Ti 2p spectrum ( Figure 2B), the peaks at 453.7, 454.1, 454.6 and 457.3 eV were attributed to Ti-C, Ti-X from Ti (Ⅱ), Ti ions with reduced charge state (TixOy) and TiO2, respectively. The peak of TiO2 indicated that Ti3C2Tx partly transformed into TiO2 nanoparticles. Furthermore, the XPS spectrum of C1s ( Figure 2C) exhibited three fitted peaks at 281.3, 284.8 and 286.6 eV, which could be assigned to C-Ti, C-C and C-O, respectively. According to the spectrum of O 1s ( Figure 2D), the binding energies at 529.8, 530.3, 531.2 and 532.5 eV could be ascribed to absorbed O species, Ti-O-Ti, Vo defect and Ti-OH [28]. These results proved the successful preparation of oxygen vacancy-rich TiO2-MXene through annealing, which played a role in providing ample active sites and then enhanced the baicalein absorption.

Electrochemical Characterizations
The electrochemically active surface area (ECSA) was one of the key factors affecting the performance of electrode materials. The ECSA of the electrode material was estimated by cyclic voltammetry (CV) measurements with different scan rates (10-80 mV·s −1 ) in 5

Electrochemical Characterizations
The electrochemically active surface area (ECSA) was one of the key factors affecting the performance of electrode materials. The ECSA of the electrode material was estimated by cyclic voltammetry (CV) measurements with different scan rates (10-80 mV·s −1 ) in 5 mM [Fe(CN) 6 ] 3−/4− containing 0.1 M KCl ( Figure 3A). The value of the specific surface area was calculated by the Randles-Sevcik equation [29]: Herein, I p represents the anodic or cathodic peak current, D (7.6 × 10 −6 cm 2 ·s −1 ) represents the diffusion coefficient, and n (n = 1) refers to the electron transfer number. A indicates the effective surface area of the working electrode, and C is the concentration of the probe molecule ([Fe(CN) 6 ] 3−/4− ). According to the peak calibration equation displayed in Figure 3B, the ECSA of TiO 2 -MXene/PEDOT:PSS was calculated to be 0.1065 cm 2 . The obtained value was much higher than that of bare GCE (0.0707 cm 2 ). The larger surface area could provide numerous active sites and reaction centers for the electrochemical redox of baicalein, thus improving the sensitivity towards baicalein detection.
was calculated by the Randles-Sevcik equation [29]: Herein, Ip represents the anodic or cathodic peak current, D (7.6 × 10 −6 cm 2 ·s −1 ) represents the diffusion coefficient, and n (n = 1) refers to the electron transfer number. A indicates the effective surface area of the working electrode, and C is the concentration of the probe molecule ([Fe(CN)6] 3−/4− ). According to the peak calibration equation displayed in Figure 3B, the ECSA of TiO2-MXene/PEDOT:PSS was calculated to be 0.1065 cm 2 . The obtained value was much higher than that of bare GCE (0.0707 cm 2 ). The larger surface area could provide numerous active sites and reaction centers for the electrochemical redox of baicalein, thus improving the sensitivity towards baicalein detection.

Electrochemical Behavior of Modified Electrodes
The electrochemical behaviors of baicalein at different modified electrodes were studied by CV measurement in 0.1 M phosphate buffer solution (PB, pH = 2.0) after accumulation in 10.0 µM baicalein for 180 s. As presented in Figure 5, there were very weak

Electrochemical Behavior of Modified Electrodes
The electrochemical behaviors of baicalein at different modified electrodes were studied by CV measurement in 0.1 M phosphate buffer (PB, pH = 2.0) after accumulation in 10.0 µM baicalein for 180 s. As presented in Figure 5, there were very weak redox peaks for the unmodified GCE (curve a), which correspond to the electrochemical redox of baicalein.

Optimizations of Analytical Parameters
To ensure the optimal analytical performance of the sensor, different experimental parameters such as the accumulation time, pH of supporting electrolyte and volume of electrode modification material were investigated.
The influence of accumulation time on the signal response of baicalein was investigated by differential pulse voltammetry (DPV). From Figure 6A, it could be found that the oxidation peak currents gradually increased when the accumulation time raised from 30 s to 180 s. However, the peak current remained stable when the time continued to increase, suggesting that the adsorption of baicalein at the TiO2-MXene/PEDOT:PSS electrode tended to be saturated. However, the longer accumulation time resulted in the prolonging of the operational time. Therefore, 180 s was selected as the most appropriate accumulation time for the following detection.
Furthermore, the volume of modified materials also affects the performance of the electrochemical sensor. The effect of the volume of the TiO2-MXene/PEDOT:PSS composite was investigated by DPV ( Figure 6B). The peak current of baicalein gradually increased as the volume of TiO2-MXene/PEDOT:PSS increased from 1 µL to 5 µL. Nevertheless, when we further increased the modifier volume, the peak current decreased, indicating that a much thicker TiO2-MXene/PEDOT:PSS composite hindered the electron transfer and inhibited the electrocatalytic activity. Thus, 5 µL was chosen as the optimum material

Optimizations of Analytical Parameters
To ensure the optimal analytical performance of the sensor, different experimental parameters such as the accumulation time, pH of supporting electrolyte and volume of electrode modification material were investigated.
The influence of accumulation time on the signal response of baicalein was investigated by differential pulse voltammetry (DPV). From Figure 6A, it could be found that the oxidation peak currents gradually increased when the accumulation time raised from 30 s to 180 s. However, the peak current remained stable when the time continued to increase, suggesting that the adsorption of baicalein at the TiO 2 -MXene/PEDOT:PSS electrode tended to be saturated. However, the longer accumulation time resulted in the prolonging of the operational time. Therefore, 180 s was selected as the most appropriate accumulation time for the following detection.  Figure 6C, the oxidation peak potential (Epa) shifted negati with the increase in pH values, which implied that protons were involved in the re reactions. Epa versus pH value presented a good linearity, with a linear regression e tion of Epa = 0.576-0.065 pH (R 2 = 0.995) ( Figure 6D). The obtained slope value mV·pH −1 ) was in proximity to the theoretical value (−59 mV·pH −1 ), suggesting that same number of electrons as protons were participating in the electrochemical reactio baicalein. Moreover, among all of the pH ranges investigated herein, the peak curre baicalein reached the maximum with PB at pH 2.0. Hence, pH 2.0 was adopted as optimal pH value of PB for the subsequent electrochemical detection.

Kinetics Studies
To investigate the redox mechanism of baicalein on TiO2-MXene/PEDOT:PSS/G the electrochemical kinetics were studied through measuring the CVs of 0.1 M of PB 2.0) with 10.0 µM of baicalein at various scan rates in the range from 25 to 300 mV·s − shown in Figure 7A, the redox currents increased significantly with the increase in rates, and the peak potentials shifted oppositely. Both the oxidation and reduction p currents displayed good linearity against the scan rates. The relationship between th dox peak current and the scan rate is shown in the inset of Figure 7B with the corresp ing linear regression equations of Ipa = 12.676 + 0.324 v (R 2 = 0.991) and Ipc = 3.567 − 0.1 (R 2 = 0.997). These experimental results indicated that the redox reaction of baicalei TiO2-MXene/PEDOT:PSS/GCE was an adsorption-controlled process.
In addition, the peak potential (Ep) versus the logarithm of scan rate (lnv) displa a good linear curve ( Figure 7C). The relevant linear regression equations were represe Furthermore, the volume of modified materials also affects the performance of the electrochemical sensor. The effect of the volume of the TiO 2 -MXene/PEDOT:PSS composite was investigated by DPV ( Figure 6B). The peak current of baicalein gradually increased as the volume of TiO 2 -MXene/PEDOT:PSS increased from 1 µL to 5 µL. Nevertheless, when we further increased the modifier volume, the peak current decreased, indicating that a much thicker TiO 2 -MXene/PEDOT:PSS composite hindered the electron transfer and inhibited the electrocatalytic activity. Thus, 5 µL was chosen as the optimum material volume for further experiments.
The effect of electrolyte pH value on the DPV response of TiO 2 -MXene/PEDOT:PSS/GCE with 10 µM baicalein was examined, as the pH of PB (0.1 M) ranged from 1.5 to 3.5. As depicted in Figure 6C, the oxidation peak potential (E pa ) shifted negatively with the increase in pH values, which implied that protons were involved in the redox reactions. E pa versus pH value presented a good linearity, with a linear regression equation of E pa = 0.576 − 0.065 pH (R 2 = 0.995) ( Figure 6D). The obtained slope value (−65 mV·pH −1 ) was in proximity to the theoretical value (−59 mV·pH −1 ), suggesting that the same number of electrons as protons were participating in the electrochemical reaction of baicalein. Moreover, among all of the pH ranges investigated herein, the peak current of baicalein reached the maximum with PB at pH 2.0. Hence, pH 2.0 was adopted as the optimal pH value of PB for the subsequent electrochemical detection.

Kinetics Studies
To investigate the redox mechanism of baicalein on TiO 2 -MXene/PEDOT:PSS/GCE, the electrochemical kinetics were studied through measuring the CVs of 0.1 M of PB (pH 2.0) with 10.0 µM of baicalein at various scan rates in the range from 25 to 300 mV·s −1 . As shown in Figure 7A, the redox currents increased significantly with the increase in scan Molecules 2023, 28, 3262 7 of 14 rates, and the peak potentials shifted oppositely. Both the oxidation and reduction peak currents displayed good linearity against the scan rates. The relationship between the redox peak current and the scan rate is shown in the inset of Figure 7B with the corresponding linear regression equations of I pa = 12.676 + 0.324 v (R 2 = 0.991) and I pc = 3.567 − 0.173 v (R 2 = 0.997). These experimental results indicated that the redox reaction of baicalein on TiO 2 -MXene/PEDOT:PSS/GCE was an adsorption-controlled process.
as Epa = 0.331 + 0.029 lnv (R 2 = 0.996) and Epc = 0.499 − 0.021 lnv (R 2 = 0.991). According to the Laviron formulas [30]: where, E 0 expresses the standard potential, α means the charge transfer coefficient and n represents electron transfer number. The values of α and n were calculated to be 0.58 and 2.1. The number of electrons in the baicalein redox reaction was equal to the number of protons [31]. The results proved that the redox reaction of baicalein on TiO2-MXene/PE-DOT:PSS/GCE was a two-electron and two-proton redox process. The theoretical redox reaction mechanism is described in Scheme 1.  In addition, the peak potential (E p ) versus the logarithm of scan rate (lnv) displayed a good linear curve ( Figure 7C). The relevant linear regression equations were represented as E pa = 0.331 + 0.029 lnv (R 2 = 0.996) and E pc = 0.499 − 0.021 lnv (R 2 = 0.991). According to the Laviron formulas [30]: where, E 0 expresses the standard potential, α means the charge transfer coefficient and n represents electron transfer number. The values of α and n were calculated to be 0.58 and 2.1. The number of electrons in the baicalein redox reaction was equal to the number of protons [31]. The results proved that the redox reaction of baicalein on TiO 2 -MXene/PEDOT:PSS/GCE was a two-electron and two-proton redox process. The theoretical redox reaction mechanism is described in Scheme 1.

Electrochemical Detection of Baicalein by DPV
Under optimal experimental parameters, the detection performance of baicalein on TiO 2 -MXene/PEDOT:PSS/GCE was measured via DPV measurement. Figure 8A revealed the DPV response of baicalein in different concentrations in 0.1 M PB (pH 2.0). It was observed that as the baicalein concentration increased, the corresponding oxidation peak currents gradually strengthened. The baicalein concentration showed positive DPV linear dependence with its oxidation peak current response from 0.007 to 10.0 µM. The relevant linear equation (Figure 8B) between the DPV peak current response and the baicalein concentration was I (µA) = 0.604 + 6.013 c (µM) with R 2 = 0.996. The LOD was calculated to be 2.33 nM (S/N = 3). To further explore the merits of TiO 2 -MXene/PEDOT:PSS/GCE, the detection limits and linear range of baicalein were compared by this system with those of previous electrochemical sensors. As shown in Table 1, the TiO 2 -MXene/PEDOT:PSS/GCE exhibited a lower LOD in contrast to the known related sensors. The excellent baicalein sensing performance of the TiO 2 -MXene/PEDOT:PSS/GCE was attributed to its high conductivity and superior adsorption ability originating from the synergies between materials.

Electrochemical Detection of Baicalein by DPV
Under optimal experimental parameters, the detection performance of baicale TiO2-MXene/PEDOT:PSS/GCE was measured via DPV measurement. Figure 8A rev the DPV response of baicalein in different concentrations in 0.1 M PB (pH 2.0). It wa served that as the baicalein concentration increased, the corresponding oxidation currents gradually strengthened. The baicalein concentration showed positive DPV l dependence with its oxidation peak current response from 0.007 to 10.0 µM. The rel linear equation (Figure 8B) between the DPV peak current response and the baicalein centration was I (µA) = 0.604 + 6.013 c (µM) with R 2 = 0.996. The LOD was calculated 2.33 nM (S/N = 3). To further explore the merits of TiO2-MXene/PEDOT:PSS/GCE, th tection limits and linear range of baicalein were compared by this system with tho previous electrochemical sensors. As shown Table 1, the TiO2-MXene/PEDOT:PSS exhibited a lower LOD in contrast to the known related sensors. The excellent baic sensing performance of the TiO2-MXene/PEDOT:PSS/GCE was attributed to its high ductivity and superior adsorption ability originating from the synergies between m als.
The superior electrocatalysis performance in the detection of baicalein on MXene/PEDOT:PSS/GCE was owing to the particular physicochemical properties of MXene and PEDOT:PSS as well as the synergy effect of TiO2-MXene/PEDOT:PSS. In s tural aspects, oxygen vacancy-rich TiO2 nanoparticles were uniformly distributed i and on the surface of MXene. The heterostructure of TiO2-MXene provided elect transport channels. Furthermore, the PEDOT:PSS film covered the surface of TiO2-MX which is beneficial for establishing connections between isolated individual TiO2-M nanosheets. The introduced PEDOT:PSS also improved the electrical conductivity o composite, thus further supporting efficient electron transmission between the baic and electrode materials. Consequently, the TiO2-MXene/PEDOT:PSS composite w new ideal electrode material for baicalein detection.

Repeatability, Reproducibility, Stability and Selectivity Studies
Repeatability, reproducibility, stability and selectivity were the basic parameters for investigating the practical capabilities of the fabricated electrochemical sensor. To assess the repeatability, one TiO 2 -MXene/PEDOT:PSS/GCE was utilized to detect 10.0 µM baicalein for fifteen repeated measurements ( Figure 9A). The relative standard deviation (RSD) was 2.07%, which showed that TiO 2 -MXene/PEDOT:PSS/GCE had a favorable repeatability. To explore the reproducibility of electrochemical sensor, ten independent TiO 2 -MXene/PEDOT:PSS/GCEs were used to determine 10.0 µM baicalein, respectively. Figure 9B suggested that the RSD was calculated to be 2.13%, indicating that the proposed sensor had good reproducibility.

Real Sample Analysis
To verify the practicability of the developed electrochemical sensor in real samples, TiO2-MXene/PEDOT:PSS/GCE was used to determine baicalein in urine samples by the standard addition method via the DPV technique. The results of the analysis of baicalein Furthermore, the stability of the prepared electrochemical electrode was investigated. The TiO 2 -MXene/PEDOT:PSS/GCE was assessed by storing the modified electrode at room temperature for one month and detecting 10.0 µM baicalein every two days. It was shown in Figure 9C that the RSD of the current response was only 1.56%, demonstrating the appreciable stability of TiO 2 -MXene/PEDOT:PSS/GCE.
Additionally, to verify the selectivity of the fabricated electrode, various potential interfering substances, including 50-fold of common ions (K + , Na + , Cu 2+ , Ba 2+ , Al 3+ , Cl − , NO 3 − , SO 4 2− ) and 50-fold of tyrosine, dopamine and ascorbic acid, were evaluated in the presence of 10.0 µM baicalein. As shown in Figure 9D, the changes in the current response of interferences were below 5%. Although the concentrations of these interfering substances were much higher than that of baicalein (10.0 µM), there was no obvious influence on the peak current of baicalein detection. The result exhibited that the TiO 2 -MXene/PEDOT:PSS/GCE possessed a reliable selectivity. Based on the above electrochemical detection, a conclusion can be drawn that the TiO 2 -MXene/PEDOT:PSS/GCE demonstrated satisfactory repeatability, reproducibility, stability and selectivity in the detection of baicalein.

Real Sample Analysis
To verify the practicability of the developed electrochemical sensor in real samples, TiO 2 -MXene/PEDOT:PSS/GCE was used to determine baicalein in urine samples by the standard addition method via the DPV technique. The results of the analysis of baicalein are summarized in Table 2. The recoveries of baicalein were in the range of 98.0 to 102.0% (n = 5), and the RSDs value were all within 3.19%. All these results demonstrated that the TiO 2 -MXene/PEDOT:PSS composite modified electrode could be efficiently applied to practical samples.   4 . All chemicals were used without any purification and the water used in this work was deionized water.

Instrumental Characterization
Scanning electron microscopy (SEM, Hitachi Company, Tokyo, Japan) and X-ray photoelectron spectroscopy (XPS, Escalab 250Xi, Thermo Fisher, Branchburg, NJ, USA) were used to understand the surface morphology and elemental composition of composite materials. All the electrochemical measurements were performed on a CHI760E electrochemical workstation (Shanghai, China). A standard three-electrode system was utilized for the electrochemical measurements, which consists of a saturated calomel electrode (SCE), a glass carbon electrode (GCE, 3 mm diameter) and a platinum wire electrode.

Synthesis of TiO 2 -MXene/PEDOT:PSS Composite
TiO 2 -MXene was prepared according to the procedure reported in the literature with slight modification [38]. Firstly, 0.2 g Ti 3 C 2 T X was heated via a tube furnace to 200 • C with a heating rate of 3 • C·min −1 in an air atmosphere and maintained for 1 h. Then, the obtained sample was further calcined to 500 • C at a rate of 5 • C·min −1 in a tube furnace under flowing N 2 and kept for 1 h. TiO 2 -MXene/PEDOT:PSS composite was fabricated by a facile ultrasound method. That is, 1.0 mL of PEDOT:PSS and 10.0 mg of the prepared TiO 2 -MXene were dispersed into 9.0 mL deionized water. The deep blue suspension was ultrasound-sonicated for 1.0 h to obtain a dispersed solution.

Preparation of Modified Electrodes
Prior to modification, the bare GCE was polished on the suede with 0.3 µm Al 2 O 3 powder, then ultrasonically cleaned three times in deionized water and ethanol, respectively, for 1 min. Subsequently, 5.0 µL of the above TiO 2 -MXene/PEDOT:PSS dispersion was drop-coated onto bare GCE and then dried under an infrared lamp to obtain TiO 2 -MXene/PEDOT:PSS/GCE. TiO 2 -MXene/GCE was manufactured in the same step (1 mg/mL TiO 2 -MXene). The synthetic process of TiO 2 -MXene/PEDOT:PSS/GCE and its sensing mechanism for the detection of baicalein were presented in Scheme 2.
photoelectron spectroscopy (XPS, Escalab 250Xi, Thermo Fisher, Branchburg, NJ, USA) were used to understand the surface morphology and elemental composition of composite materials. All the electrochemical measurements were performed on a CHI760E electrochemical workstation (Shanghai, China). A standard three-electrode system was utilized for the electrochemical measurements, which consists of a saturated calomel electrode (SCE), a glass carbon electrode (GCE, 3 mm diameter) and a platinum wire electrode.

Synthesis of TiO2-MXene/PEDOT:PSS Composite
TiO2-MXene was prepared according to the procedure reported in the literature with slight modification [38]. Firstly, 0.2 g Ti3C2TX was heated via a tube furnace to 200 °C with a heating rate of 3 °C·min −1 in an air atmosphere and maintained for 1 h. Then, the obtained sample was further calcined to 500 °C at a rate of 5 °C·min −1 in a tube furnace under flowing N2 and kept for 1 h.
TiO2-MXene/PEDOT:PSS composite was fabricated by a facile ultrasound method. That is, 1.0 mL of PEDOT:PSS and 10.0 mg of the prepared TiO2-MXene were dispersed into 9.0 mL deionized water. The deep blue suspension was ultrasound-sonicated for 1.0 h to obtain a dispersed solution.

Preparation of Modified Electrodes
Prior to modification, the bare GCE was polished on the suede with 0.3 µm Al2O3 powder, then ultrasonically cleaned three times in deionized water and ethanol, respectively, for 1 min. Subsequently, 5.0 µL of the above TiO2-MXene/PEDOT:PSS dispersion was drop-coated onto bare GCE and then dried under an infrared lamp to obtain TiO2-MXene/PEDOT:PSS/GCE. TiO2-MXene/GCE was manufactured in the same step (1 mg/mL TiO2-MXene). The synthetic process of TiO2-MXene/PEDOT:PSS/GCE and its sensing mechanism for the detection of baicalein were presented in Scheme 2.

Electrochemical Measurement
Electrochemical impendence spectroscopy (EIS) measurements were investigated in 5.0 mM [Fe(CN) 6 ] 3−/4− containing 0.1 M KCl with a frequency from 1 to 10 5 Hz, and the amplitude was 5 mV. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) measurements were used to investigate the electrochemical behaviors of a series of electrodes in 0.1 M PB, with a potential range of 0.1 to 0.7 V and at a scan rate of 100 mV·s −1 .

Preparation of Real Samples
The urine samples were collected from healthy volunteers. The obtained urine sample was filtered by a 0.45 µm pore-size nylon filter and diluted with 0.1 M PB (pH = 2.0) 100 times. Baicalein samples with known standard concentrations were used to spike the urine samples for the real sample analysis using the standard addition method.

Conclusions
In summary, our work reported a novel electrochemical sensing platform for baicalein determination, which was developed on the grounds of the synergistic mechanism between TiO 2 -MXene and PEDOT:PSS. The TiO 2 -MXene/PEDOT:PSS composite presented high conductivity, a large electroactive surface area, and superior electrocatalytic activity, which were effective for electron transfer and the adsorption of baicalein. Based on these characteristics of the composite material, the established electrochemical sensor also exhibited a wide linear response of 0.007-10.0 µM and a low LOD of 2.33 nM. At the same time, the as-prepared electrode demonstrated excellent repeatability, reproducibility and stability for the detection of baicalein. Additionally, this sensor further demonstrated its satisfactory detection ability in human urine samples, which presented good spiked recoveries, indicating great potential application prospects in the electrochemical detection of baicalein.

Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.

Data Availability Statement:
The data presented in this study are available in the article.