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. 2025 Jun 11;19(24):22007–22016. doi: 10.1021/acsnano.5c00864

Synthesis of Ti2CO2 MXene and Its Application in Photoelectrochemical Biosensors with Ultrahigh Sensitivity and Long-Term Stability

Yang Li †, Fei Cheng †,*, Yaqin Qi †, Kaiyun Chen ‡, Jiaxin Peng †, Jing Zhao †, Fengqiu Jiang §, Rui Xu ∥
PMCID: PMC12204091  PMID: 40497813

Abstract

Theoretical chemists have predicted that Ti2CO2 is a promising semiconducting MXene with high stability and surface activity, making it suitable as the bonding layer in biosensors. However, its synthesis remains challenging due to difficulties in accurately controlling the oxidation of the initial Ti2C phase. Here, we successfully synthesized Ti2CO2 MXene via pulsed ozone treatment (POT). The resulting Ti2CO2 MXene is an n-type semiconductor with a bandgap of 0.49 eV, exhibiting a high probe adsorption capacity of ∼3.03 × 1014 molecules/cm2. The successful synthesis of Ti2CO2 MXene is attributed to a strategy of controlling the activation energy window during the “Ti2C → Ti2CO2 → TiO2” multistep reaction. The strong oxidizing ability of ozone reduces the activation energy barrier for the “Ti2C → Ti2CO2” reaction, while precise control of short-time POT pulses inhibits the formation of TiO2. By employing the Ti2CO2 MXene as a bonding layer in a photoelectrochemical sensor for serotonin detection, the sensor exhibits an ultrahigh sensitivity of 0.433 aM (oligomolecular level) and considerable long-term stability for over 240 h. Given its high adsorption capacity and robust long-term stability, Ti2CO2 MXene becomes a positive candidate for high-precision biosensing applications.

Keywords: synthesis, MXene, photoelectrochemical, biosensor, high sensitivity, stability

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Rapid growth and high acceptance of portable biosensors are facilitated by a huge demand for various monitoring services in ubiquitous areas such as personal health monitoring, food/pharmaceutical quality control, environmental monitoring, and human-machine interaction, making them the largest segment ($23.5 billion in 2023) in the global sensor industry. − Electrochemical biosensors, in particular, are cornerstone technologies that directly influence approximately 70% of medical decisions through timely and precise biochemical measurements, leading to an urgent need for further innovations. , Both electrochemical sensors and their advanced derivatives, photoelectrochemical (PEC) sensors, are typically structured with inorganic–organic interfaces. They comprise a biorecognition element (e.g., probes), a transducer (e.g., electrodes), and a bonding layer (biocompatibility materials/chemical groups), as illustrated in Figure a. In this configuration, the bonding layer plays a pivotal role in adsorbing and stabilizing the bioprobes, facilitating their connection to the electrodes, and enabling the recognition, transport, and amplification of charge signals. The development of bonding materials that are biocompatible, easy to fabricate, stable, and strongly adhesive remains a persistent scientific and engineering challenge, aimed at improving the selectivity, stability, and sensitivity of biosensors.

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(a) Applications of different types of electrochemical biosensors in human health monitoring; (b) comparison of the probe adsorption capacity (probe density) and long-term stability of the Ti2CO2 MXene-based biosensor with various biosensors assembled by typical bonding materials. −

Current bonding materials used in electrochemical biosensors include precious metals, carbon-based composites, transition-metal derivatives, and self-assembled monolayers. , Among these, surface-modified gold nanoparticles are widely utilized due to their chemical stability and high probe adsorption capacity. − However, their unpredictable biological toxicity after modification may compromise the long-term usability of biosensors. , Additionally, these metal nanoparticles intrinsically tend to aggregate when exposed to external stimuli (electric fields, magnetic fields, light, and so forth) due to surface plasmon resonance, charge rearrangement, and electrophoretic effects. This results in an unstable spatial distribution of nanoparticles, thereby significantly diminishing the sensitivity and long-term stability of the biosensors. Two-dimensional semiconductor materials, such as graphene, transition-metal dichalcogenides, black phosphorus, hexagonal boron nitride, and semiconducting MXenes, might emerge as promising candidates to solve these challenges in metal-based bonding layers. − Their relatively stable spatial distribution under external stimuli contributes to enhanced long-term stability of biosensors. Notably, to facilitate adsorption and stabilization of bioprobes, the surfaces of these bonding materials must be readily functionalized with various groups. Accordingly, MXenes (M n+1X n T x , where M = transition metal, X = C and/or N, and T = surface termination) are attractive because they naturally possess a variety of terminations (−O, −F, −OH, and so forth). In particular, MXenes predominantly terminated with oxygen groups (−O), such as Ti3C2O2, have been widely reported for sensing applications, due to their considerable hydrophilicity and biocompatibility. , Typically, single-layer Ti3C2O2 MXene exhibits metallic behavior with a high electrical conductivity of 104–105 S cm–1, whereas multilayer or surface-modified Ti3C2O2 MXene may exhibit semiconducting-like characteristics. Such semiconducting MXenes not only exhibit high carrier mobility but also possess abundant surface functional groups for probe adsorption, increasing the intrinsic affinity for specific biomolecules and resulting in improved sensitivity. ,

However, many MXenes suffer from limited chemical stability. They are easy to be oxidized in air or solution, as their bare metal surfaces are not fully protected by antioxidative terminations. Even for the best biosensors employing MXene-based bonding layers, the functional time is typically short, often less than approximately 120 h. , To preserve the metal framework and maintain long-term functionality, covalent grafting of antioxidative surface groups is essential. Ti2CO2 MXene, theoretically predicted over a decade ago, is a two-dimensional semiconductor uniformly covered by oxygen-containing surface groups, conferring exceptional biocompatibility and stability. ,,, Moreover, it is theoretically calculated to possess an intrinsically stable band structure and an ultrahigh carrier mobility of up to 104 cm2 V–1 s–1 at room temperature, vastly exceeding that of Ti3C2T x MXene (∼0.7 cm2 V–1 s–1), MoS2 (400 cm2 V–1 s–1), black phosphorus (90.70–155.33 cm2 V–1 s–1), and other typical 2D materials. , These features are highly advantageous for accelerating the response kinetics and boosting the sensitivity of PEC sensors. It would be great progress for the biosensors to develop and synthesize long-term stable Ti2CO2 MXene-based bonding materials while remaining large probe adsorption capability, ultimately achieving ultrahigh sensing performance.

Synthesizing Ti2CO2 MXene remains challenging due to difficulties in precisely controlling the oxidation of the intermediate Ti2C phase after conventional wet-chemical etching of Ti2AlC, which often leads to the undesired formation of TiO2. In this study, we achieved the experimental synthesis of stable Ti2CO2 MXene via pulsed ozone treatment (POT), enabling precise regulation of surface functional groups and oxidation kinetics of Ti2C. The resulting Ti2CO2 MXene is an n-type semiconductor with a narrow bandgap (0.49 eV) and an extensive specific surface area (208.54 m2/g). Additionally, it demonstrates a high probe adsorption capacity of ∼3.03 × 1014 molecules/cm2 for serotonin (5-HT, an important biomarker of mental illness) and maintains exceptional photocurrent stability (∼240 h). When applied in detecting serotonin and other biomarkers with similar molecular structures, Ti2CO2 MXene exhibits superior comprehensive performance (including both adsorption activity and stability) as a bonding material in electrochemical biosensors (Figure b). − The PEC biosensor employing Ti2CO2 MXene bonding materials for serotonin detection has reached an ultrahigh sensitivity of 0.433 aM (oligomolecular level). Importantly, the ultrahigh sensitivity demonstrates exceptional stability, exhibiting only 5% photocurrent decay after 240 h, ranking among the best-reported performances. With its intrinsic biocompatibility, as well as the developed high adsorption capability and remarkable stability, Ti2CO2 MXene emerges as an ideal candidate for real-time, high-precision biosensing applications.

Results

The key enabler for preparing Ti2CO2 MXene is carefully controlling the oxidation of the Ti2C phase via pulsed ozone treatment (POT). As illustrated in Figure a, few-layer Ti2C MXene was obtained through delamination of the Ti2AlC precursor (Figure S1), followed by being placed in a custom-made powder tray and covered with a 500-mesh copper net. The chamber pressure was maintained below 1 × 1 × 10–4 Pa to ensure a high-purity initial atmosphere. Through systematic optimization of POT parameters, such as ozone pulse time, purge interval, frequency, and so forth, the oxidation of Ti2C could be accurately tuned. A high-quality Ti2CO2 phase was successfully synthesized using POT for 50 cycles, with an ozone pulse time of 30 ms, a purge time of 5 s in each cycle, and a 2 s wait between each cycle at 50 °C (in Figure S1). This synthesis is primarily evidenced by the X-ray diffraction (XRD) patterns before and after POT, as depicted in Figure b. The untreated sample displays no distinct XRD peaks, indicating the successful removal of Al atoms from Ti2AlC and the formation of pure Ti2C. In contrast, the POT-treated sample displays characteristic peaks at 25.4°, 35.8°, 37.1°, and 47.9°, matching the predicted Ti2CO2 lattice parameters calculated by density functional theory (DFT). The TEM image in Figure c (left) shows that the sample remains in the few-layer configuration after multiple short POT, while the EDS mapping reveals an oxygen-rich state and a uniform distribution of oxygen functional groups across the surface (Figure S4 in Supporting Information). The structure and morphology results of the POT-treated sample confirm the successful synthesis of Ti2CO2 MXene. Additionally, Ti2CO2 MXene layers can be further processed to meet specific functional requirements. For instance, Ti2CO2 quantum dots (QDs), synthesized via further hydrothermal treatment, as shown in Figure c (right), offer advantages for applications in optical sensing and high-sensitivity fluorescent biosensors.

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(a) Schematic diagram of the synthesis process of Ti2CO2 MXene; (b) XRD patterns of samples before and after POT; and (c) TEM images at different scales after POT.

The semiconducting characteristics of the synthesized Ti2CO2 and untreated Ti2C, including their electronic states and chemical bonds, were further analyzed in Figure . Under a 980 nm infrared irradiation, the untreated Ti2C exhibits an irresponsive photocurrent, whereas the Ti2CO2 MXene generates a photocurrent of 1.09 μA/cm2 upon illumination (Figure a). Furthermore, ultraviolet–visible (UV–vis) spectroscopy analysis in Figure b shows a typical metallic absorption for untreated Ti2C and a significant reduction in absorbance for the POT-treated Ti2CO2 sample, indicating its semiconductor nature. The synthesized Ti2CO2 shows an absorption edge at 2500 nm and a bandgap (E g) of 0.49 eV, consistent with DFT predictions (0.42 eV, Figure S4 in Supporting Information). Hall effect measurements for both Ti2C and Ti2CO2 MXenes are further detailed in Table . The untreated Ti2C and synthesized Ti2CO2 exhibit completely different electrical properties. Untreated Ti2C demonstrates metallic behavior with low resistivity (6.895 × 10–4 Ω cm) and high carrier concentration (1.833 × 1020 cm–3), while POT-treated Ti2CO2 displays semiconductor characteristics with higher resistivity (2.772 × 105 Ω cm) and a drastically reduced carrier concentration (4.612 × 108 cm–3). These results conclusively demonstrate that the synthesized Ti2CO2 is an n-type narrow-bandgap semiconductor, aligning with computational predictions (Figure S3).

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(a) Photoelectric current test results for Ti2C and Ti2CO2; (b) UV–vis absorption spectra for Ti2C and Ti2CO2 (spanning the wavelength range of 250 to 2500 nm), with an inset showing the band structure diagrams of Ti2C and Ti2CO2; (c) FT-IR spectrum of Ti2C and Ti2CO2; and (d) X-ray photoelectron spectroscopy (XPS) fittings for classic (d1) Ti 2p, (d2) C 1s, and (d3) O 1s.

1. Hall Effect Measurements for the Untreated Ti2C and POT-Treated Ti2CO2 Sample .

results explanation Ti2C Ti2CO2
μH Hall mobility (cm2 v–1 s–1) 49.368 4.881 × 104
CT carrier type P N
n carrier concentration (cm–3) 1.833 × 1020 4.612 × 104
n sheet sheet carrier concentration (cm–3) 9.157 × 1015 2.306 × 104
R H Hall coefficient (cm3 C–1) 3.404 × 10–2 1.353 × 104
R Hsheet sheet hall coefficient (cm3 C–1) 6.808 × 102 2.706 × 1014
ρ resistivity (Ω cm) 6.895 × 10–4 2.772 × 105
ρsheet sheet resistivity (Ω/□) 13.791 5.544 × 109
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a

Notes: the Hall effect was tested with an Lp of 5 mm, a Hall factor of 1, a maximum voltage of 20 V, a maximum current of 20 mA, and a gate bias voltage of 0 V.

The chemical bond characteristics of untreated Ti2C and POT-treated Ti2CO2 were analyzed via Fourier-transform infrared spectroscopy (FT-IR) in Figure c. The spectrum of untreated Ti2C shows only a weak CO absorption peak, characteristic of pure Ti2C. After POT, new absorption peaks emerge at 1000 cm–1 (C–Ti–O lattice vibration) along with Ti–O and CO nonintrinsic dangling bonds, indicating titanium valence changes during POT. This bonding evolution suggests that the formation of Ti2CO2 MXene is driven through the extension of C–Ti–O bonds into a two-dimensional plane, consistent with DFT-predicted results.

High-resolution X-ray photoelectron spectroscopy (XPS) further elucidates the characteristics of Ti 2p, C 1s, and O 1s orbitals in untreated Ti2C and synthesized Ti2CO2, as shown in Figure d. The Ti 2p orbitals for Ti2C (Figure d1) display a characteristic peak of the Ti–C bond (Ti2+) at 455.5 eV, and a Ti-X bond (Ti2+, X = O or other elements) at 456.5 eV, suggesting that titanium has a valence of +2 in Ti2C. After POT, new characteristic peaks appear at 459.5 and 457.5 eV, corresponding to completely oxidized Ti4+ and a few possible incompletely oxidized Ti3+ in the synthesized Ti2CO2. These characteristics indicate a transition from Ti2+ to higher oxidation states. Moreover, the C 1s XPS spectrum (Figure d2) shows that the Ti–C bond near 281 eV in Ti2C gradually disappears during POT, while a new peak of the C–Ti–O bond emerges at 284.4 eV. This indicates that the valence change of titanium is ascribe to the oxidization of the Ti–C bond during POT. Additionally, the O 1s XPS spectrum (Figure d3) reveals a characteristic peak at 530.3 eV, indicating the involvement of oxygen atoms in forming C–O bonds. In short, the evolution of each orbital spectrum confirms the formation of Ti2CO2 from Ti2C via POT.

Discussion

The strong oxidizing ability of ozone coupled with precise oxidation control of initial Ti2C via short-time pulses are two critical factors for synthesizing Ti2CO2 MXene. To elucidate the synthesis mechanism of Ti2CO2 via POT, we employed transition state theory within first-principles calculations to evaluate energy states and valence bond evolutions throughout the multistep reaction of “Ti2C → Ti2CO2 → TiO2”. Initial Ti2C is oxidized under specific conditions, namely, vacuum ozone conditions (Figure a1,b left) and vacuum oxygen conditions (Figure a2,b right). These conditions lead to distinctly different reaction products, namely, Ti2CO2 under ozone and TiO2 under oxygen.

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(a) Reaction pathway diagram illustrating the interaction of Ti2C with ozone (O3) and oxygen (O2); (b) mechanism diagram showing the detailed reaction steps of Ti2C with ozone (O3) and oxygen (O2).

Under vacuum ozone (O3) conditions (Figure a1), the activation energy for the formation of Ti2CO2 from the initial Ti2C is only 3.46 eV (ΔE 2), which is significantly lower than that for directly forming TiO2 from Ti2C (ΔE 1 = 8.70 eV). The “activation energy window” (ΔE W = ΔE 1 – ΔE 2) between the above two reactions exhibits a significant positive difference of 5.24 eV. Such a large ΔE W creates a thermodynamic preference for intermediate Ti2CO2 formation when the O3 flux is precisely regulated. Furthermore, the prohibitively high activation energy (ΔE 3 = 11.91 eV) for converting intermediate Ti2CO2 to TiO2 effectively suppresses unwanted overoxidation. As shown in Figure b, the evolution of valence bonds during the reactions under O3 conditions further elucidates the mechanism for synthesizing Ti2CO2 MXene via POT. Ozone (O3) exhibits significantly high oxidative activity, enabling it to generate highly reactive oxygen atoms (monatomic oxygen), which preferentially combine with surface Ti atoms of the initial Ti2C. The formation of Ti–O bonds typically induces a partial rearrangement of the existing Ti–C bonds while preserving the overall Ti–C skeleton. In this case, the formation of Ti–O bonds occurs through an “intercalation” process, allowing both Ti–O and Ti–C bonds to coexist. Such “intercalation” coincides with the low activation energy of 3.46 eV (ΔE 2) for the “Ti2C → Ti2CO2” reaction in Figure a, which can occur at a relatively low temperature of 323 K. Once Ti2CO2 MXene reaches saturation, it becomes stable, as its surface-dangling O atoms repel the external O atoms even at high temperatures (up to 550 °C), thus inhibiting further oxidation to TiO2. This is reflected in the large activation energy of 11.91 eV (ΔE 3) for the “Ti2CO2 → TiO2” reaction in Figure a. As previously predicted, fully oxygen-terminated Ti2CO2 is the most thermodynamically favorable structure across a wide range of oxygen chemical potentials (from −4 to 0 eV), ensuring its ambient stability.

In contrast, under vacuum oxygen (O2) conditions (Figure a2), the activation energy for the “Ti2C → Ti2CO2” reaction (ΔE′2= 8.85 eV) closely matches that for the “Ti2C → TiO2” (ΔE′1 = 8.52 eV) reaction. The resultant activation energy window (ΔE′W = ΔE′1 – ΔE′2 = −0.33 eV) between the above two reactions is negative, indicating that the formation of intermediate Ti2CO2 is less thermodynamically favorable compared to the direct formation of TiO2. This is attributed to the high dissociation energy of O2 molecules and the decomposition of Ti–C bonds. ,, The dissociated O atoms on the Ti2C surface tend to form superoxol/peroxo species that directly react to produce Ti2CO x , eventually leading to the formation of energy-stable TiO2 without significant energy barriers, corresponding to the lower activation energy (ΔE′1) for the “Ti2C → TiO2” reaction. Such thermodynamic considerations also explain why certain carbon-based MXenes (e.g., Ti2C and Ti3C2) inevitably oxidize to TiO2 under ambient oxygen exposure.

In short, it is an effective and universal method for synthesizing metastable MXenes by tuning the activation energy window via the POT at near room temperature. On the one hand, the initial reactants remain stable and inert at relatively low temperatures, suppressing unexpected decomposition or uncontrolled side reactions. On the other hand, the highly active O3 reduces the energy barrier for synthesizing the intermediate products (such as Ti2CO2) and broaden the ΔE W to stabilize the intermediate products against overoxidation. Even after prolonged exposure to the POT cycles, the synthesized Ti2CO2 remains stable, as evidenced in Figure S1.

Due to the unique surface chemistry and electronic band structure features, the synthesized Ti2CO2 MXene emerges as an outstanding candidate for the fabrication of PEC biosensors. , Unlike MXenes terminated with −F or −OH groups, Ti2CO2 MXene is exclusively terminated with oxygen groups (−O), which boosts its oxidation resistance and greatly enhances both its stability and biocompatibility. Moreover, Ti2CO2 MXene is a narrow-bandgap semiconductor that can be excited by infrared light (a wavelength that minimizes damage to biomolecules). These combined advantages render Ti2CO2 MXene exceptionally well suited for biomedical therapies and PEC biosensing applications. For instance, clinical studies have demonstrated that monoamine neurotransmitters in blood, such as serotonin (5-HT), serve as key biomarkers for depression. , Accurate monitoring of 5-HT is, therefore, crucial for developing precise, multidimensional diagnostic strategies for depression. However, 5-HT in blood is at low abundance (on the order of fg/mL to pg/mL levels) and exhibits only subtle fluctuations between healthy and depressed individuals, making precise detection of 5-HT extremely challenging. Here, to address these challenges, an integrated three-electrode PEC biosensor based on Ti2CO2 MXene was designed, achieving ultrahighly sensitive 5-HT detection with robust long-term stability, as illustrated in Figure a.

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(a) Schematic diagram of an integrated Ti2CO2 PEC biosensor structure; (b) chronocoulometric measurement of probe adsorption density, with the inset showing the calculated adsorption results of 5-HT probes on Ti2C and Ti2CO2; (c) calculated adsorption energy of four nucleic acid bases by varies bonding materials; ,− (d) selectivity/specificity of the Ti2CO2 MXene-based biosensor in PBS (pH 7.4) and the mouse serum, respectively; (e) comparison of the operational stability of Ti2C and Ti2CO2 photoanodes in PBS (pH 7.4), demonstrating the superior long-term stability of Ti2CO2 (>240 h); (f) long-term stability of Ti2CO2 under different ambient temperatures and different light illumination intensities; (g) photocurrent response for different concentrations of 5-HT in PBS; (h) linear calibration curve for different concentrations of 5-HT in PBS, and the inset is the linear calibration curve for different concentrations of 5-HT in mouse serum matrices; and (i) comparison of checkout sensitivity for 5-HT detection with different methods. ,,−

A transparent indium tin oxide (ITO) glass substrate was patterned with etched electrodes, followed by spray-coating Ti2CO2 onto the working electrode as the bonding layer. Specific aptamer probes targeting the neurotransmitter 5-HT (an important biomarker for mental illness diagnostics) were dropped onto the surface of the working electrode and incubated for a defined period. These probes were anchored onto the Ti2CO2 bonding layer, enabling charge transfer and photoelectrical detection. The sensor was then immersed in phosphate-buffered saline (PBS) solution and exposed to pulsed infrared light excitation. As a result, the n-type semiconducting Ti2CO2 layer can generate photocurrent upon illumination. The 5-HT in solution is captured by the aptamers, inducing redox reactions that modulate the photocurrent intensity proportionally to the analyte concentration and enable quantitative detection of 5-HT. , For comparison, a control biosensor using Ti2C as the bonding layer was fabricated.

The Ti2CO2 bonding layer exhibits two major advantages: considerable probe adsorption capability and outstanding long-term stability. The biosensor with the Ti2CO2 bonding layer achieves a probe adsorption density of 1.07 × 1014 molecules/cm2, which is dramatically 72 times higher than that with the Ti2C bonding layer, as shown in Figure b. This enhancement arises from the larger surface area of Ti2CO2 MXene (2.97 times greater than that of untreated Ti2C, as shown in Figure S7 in the Supporting Information) and its abundance of active functional groups. The adsorption energies of Ti2CO2 and Ti2C MXenes for the adsorption of nucleic acid bases (i.e., A, G, T, and C) were further calculated using DFT (Figure S8 in Supporting Information). Ti2CO2 MXene exhibits exceptionally high adsorption energy (in absolute terms), surpassing those of representative two-dimensional biomaterials, as shown in Figure c. ,− These results confirm the superior adsorption capability of Ti2CO2 MXene to anchor diverse aptamer bases. In addition, fluorescence microscopy images demonstrate homogeneous distribution of fluorophore-labeled 5-HT aptamer probes on the surface of the Ti2CO2 bonding layer (Figure S9 in the Supporting Information), while chronocoulometric measurements validate that the Ti2CO2 MXene-based sensor exhibits the optimal probe adsorption density (Figure S9 in the Supporting Information). Thus, both computational and experimental results underscore the exceptional adsorption performance of Ti2CO2 MXene, enabling sufficient anchoring of specific 5-HT aptamer probes to enhance the selectivity of biosensors.

To evaluate the selectivity and robustness of the Ti2CO2 MXene-based PEC biosensor for 5-HT detection, controlled samples containing dopamine (DA), histamine (HA), carbohydrate antigen 125 (CA125), and bovine serum albumin (BSA) at 1pg/mL concentrations were tested. As shown in Figure d, the biosensor exhibits specific photocurrent responses to 5-HT amidst these interferents in both PBS and mouse serum solution. Even when exposed to mixtures of 5-HT, DA, and HA in PBS (or mouse serum), a remarkable photocurrent response can also be observed, confirming the excellent selectivity for 5-HT of the biosensor under complex biological conditions. Meanwhile, the sensor with the Ti2CO2 bonding layer maintains an exceptional long-term stability for up to 240 h (photocurrent decay < 5%) at a bias potential of 1.23 V (vs RHE) in PBS, as shown in Figure e. Such performance significantly exceeds that of currently reported MXene-based biosensors, rivaling commercial gold-based biosensors, as shown in Figure . − Even under environmental fluctuations (such as an ambient temperature range from 5 to 50 °C, or a laser illumination intensity range from 0.15 to 0.6 W/cm2), the Ti2CO2 MXene-based biosensor consistently exhibits excellent long-term stability (>200 h), as shown in Figure f, along with remarkable antiaging performance (as shown in Figure S6).

Due to its ultrahigh probe adsorption capacity, oxygen-rich dangling bonds, and high carrier mobility, the Ti2CO2 MXene bonding layer enables the biosensor to achieve an exceptionally limit of detection (LOD = 3N/S, i.e., checkout sensitivity) of 0.33 fg/mL and a very wide linear range spanning from fg/mL to ng/mL levels, as shown in Figure g,h. Such good checkout sensitivity far exceeds that of other 5-HT detection biosensors reported before (Figure i), leading to an outstanding detection level of oligomolecular. ,,− More importantly, the biosensor maintains ultrahigh sensitivity and nanogram-level resolution in detecting 5-HT within mouse serum matrices, highlighting its exceptional potential for real-world biomarker monitoring (Figure h). Additionally, Ti2CO2 MXene-based biosensors are activated by infrared light, which minimizes potential damage to biomolecules from shorter wavelengths, thereby reducing corresponding measurement inaccuracies.

Hence, the Ti2CO2 MXene-based biosensors demonstrate excellent biocompatibility, high sensitivity, and long-term stability, greatly expanding their potential for applications in environmental monitoring and medical diagnostics. The unique properties of Ti2CO2 MXene make it an advanced biosensing material, which is not only suitable for current PEC biosensors but also promising for future applications in advanced biosensing technologies, such as single-molecule detection, cellular imaging, and real-time biological analysis.

Conclusions

In summary, we successfully demonstrated the synthesis of Ti2CO2 MXene by employing POT, a strategy of controlling the activation energy window during the “Ti2C → Ti2CO2 → TiO2” multistep reaction. The synthesized Ti2CO2 is an n-type semiconductor with a bandgap of 0.49 eV, achieving a high probe adsorption capacity of ∼3.03 × 1014 molecules/cm2. Furthermore, we explored its application in PEC sensors for serotonin detection. The Ti2CO2 MXene-based biosensor achieves an ultrahigh sensitivity of 0.433 aM (oligomolecular level) and considerable long-term stability for over 240 h. The high adsorption capacity and robust long-term stability make Ti2CO2 MXene an ideal candidate for real-time and high-precision biosensing applications.

Materials and Methods

Materials and Reagents

Ti2AlC (99%, ∼300 mesh), hydrofluoric acid (HF, 99%), ethylene glycol (C2H6O2, >99%), dimethyl sulfoxide (DMSO, C2H6SO, >99.8%), and ammonium hydroxide solution (NH3·H2O, 25–28%) were obtained from Macklin Chemical Reagent Co., Ltd., China. Polytetrafluoroethylene (PTFE) membrane filters (hydrophilic PTFE, pore size: 0.1–1 μm) were obtained from Xin Xing Co., Ltd., China. Milli-Q grade water was used in all experiments (Millipore water purification system Z18 MΩ, Milli-Q, Millipore, Billerica, MA). Phosphate-buffered saline (PBS, 0.1 M, pH = 7.4) and DNA aptamers (the sequence of 5′- CTC TCG GGA CGA CTG GTA GGC AGA TAG GGG AAG CTG ATT CGA TGC GTG GGT CGT CCC -3′) were obtained from Shanghai Sangon Biotech Co., Ltd., China. Indium tin oxide (ITO)-coated glass (10 × 20 × 0.5 mm, sheet resistance <10 Ω/□) was obtained from Luoyang Guluo Co., Ltd., China. Mouse serum was obtained from Henan Yiqi Biotechnology Co., Ltd.

Synthesis of Ti2C

First, 2.5 g of Ti2AlC powders were dispersed in 250 mL of HF solution (40 wt %) and stirred at 32 °C for 24 h. After filtration, the resulting black powder was washed with ultrapure water until the pH of the supernatant was above 6, with intermediate centrifugation at 8000 rpm for 5 min to clarify the liquid. The Ti2C MXene flakes were then obtained after being dried at 80 °C under vacuum for 12 h.

Intercalation of Ti2CT x

One g of Ti2C flakes (1 g) were dispersed into 100 mL of dimethyl sulfoxide (DMSO), and the mixture was stirred at 25 °C for 120 h to increase the interlayer spacing of the flakes. Afterward, the suspension was centrifuged, and the resulting precipitate was washed several times with deionized water until all DMSO was completely removed. The Ti2CT x powders were then obtained by drying at 60 °C in a vacuum oven for 6 h.

Synthesis of Fewer-Layer Ti2CT x

0.5 g of Ti2CT x powders were dispersed into 500 mL of ultrapure water under continuously bubbled nitrogen. The mixture was subsequently ultrasonicated for 6 h at a temperature not exceeding 10 °C, followed by additional ultrasonication for 15–20 min. The filtered precipitate was dried at 60 °C in a vacuum oven for 6 h to obtain multilayered Ti2CT x powders.

Synthesis of Multilayered Ti2CO2

The multilayered Ti2CO2 was synthesized via pulsed ozone treatment (POT). Specifically, 0.2 g of multilayered Ti2CT x powders were placed in a custom-made powder tray and covered with a 500-mesh copper net. The initial chamber pressure was maintained below 1 × 10–4 Pa, and the chamber temperature was kept at 50 °C. Ozone was introduced into the chamber for 30 ms and purged for 5 s in each cycle, with a 2 s wait between each cycle. By adjustment of the number of cycles, Ti2CO2 MXene was obtained. Additionally, 10 mg of Ti2CO2 powders was ultrasonically treated for 2 h in 100 mL of ultrapure water. Then, the dispersed mixture was filtrated through a filter membrane with 50 nm pores to obtain Ti2CO2 quantum dots.

Fabrication of the Ti2CO2 MXene-Based Photoelectrochemical Biosensor

As shown in Figure S2, 1 mg of Ti2CO2 MXene powder was dispersed in 10 mL of ultrapure water, followed by ultrasonic dispersion. Subsequently, 1 mL of the well-dispersed Ti2CO2 turbid liquid was directly sprayed onto the working electrode area of the etched ITO glass and then dried at 60 °C for 10 min. Next, 10 μL of 3 μM 5-HT aptamers were dropped onto the surface of the working electrode and incubated at 37 °C for 2 h. Similarly, as shown in Figure S3, to facilitate the scale-up of biosensor fabrication, a 4 in. ITO glass substrate was etched to create 21 pieces of three-electrode configurations, which were subsequently coated with Ti2CO2 layers via spray deposition. Such a batch fabrication process minimizes unnecessary losses of the Ti2CO2 turbid liquid, reducing its average consumption to ∼0.4 mL/piece (namely, 40 μg/piece). As a result, 200 mg of Ti2CO2 powder prepared in a single POT process is sufficient to fabricate up to 5000 pieces of PEC biosensors, approaching pilot-scale production levels. The working electrode was then washed with PBS; thus, the Ti2CO2 MXene-based PEC biosensor was fabricated. All electrodes were immersed in 1 mL of different concentrations of 5-HT solutions for 45 min, and the surface of the sensors was thoroughly washed with PBS to remove any unhybridized target 5-HT.

Characterizations and Photoelectrochemical Performance Measurements

The microstructure of Ti2CO2 was observed by using a high-resolution transmission electron microscope (HRTEM, Tecnai G2 F30, FEI, USA). The light absorption range of the Ti2C and Ti2CO2 series was analyzed using a UV–vis diffuse reflectance spectrophotometer (UV–vis DRS, TU-1901, Puxi, Beijing). Fourier-transform infrared (FT-IR) spectra were recorded using a Nicolet iS5 FT-IR spectrometer (Thermo Scientific, USA). The crystalline structures of Ti2C and Ti2CO2 were identified by X-ray diffraction (XRD, D/MAX-2500/PC, Rigaku, Japan). Surface chemical states and compositions of Ti2C and Ti2CO2 were analyzed by using X-ray photoelectron spectroscopy (XPS, Kratos AXIS SUPRA, UK). Hall effect measurements were conducted using a Keithley 4200 semiconductor parameter analyzer (Keithley Instruments, USA). Photoelectrochemical performance was evaluated using a CHI660E electrochemical workstation (CH Instrument, Shanghai, China) in a standard three-electrode system, with 0.1 M of PBS (pH 7.4) as the electrolyte, employing a Ag/AgCl reference electrode and a platinum counter electrode.

[Further details of the crystal structure investigation may be obtained from the Materials Project via next-gen.materialsproject.org/].

Supplementary Material

nn5c00864_si_001.pdf (911.2KB, pdf)

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant Nos. 62301446 and 12204383), the Basic Pre Research Project of Xi’an Rare Metal Materials Institute Co., Ltd (Preresearch project) (No. Y2208S), the Program for Young Scientific New-Star in Shaanxi Province of China (No. S2025-ZC-2-0190), and the Young Elite Scientists Sponsorship Program by CAST (2023QNRC001).

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.5c00864.

  • Photoelectric responses, detailed images of electrodes, DFT calculations, TEM images and EDS mappings of Ti2CO2 MXene; characterization of long-term stability, adsorption capacity, adsorption energy and fluorescence microscope morphologies of Ti2CO2 MXene-based biosensors, and other control experiments (PDF)

Y.L. and F.C. conceived the idea of the project and wrote the manuscript with input from all coauthors. Y.L. designed and performed the experiments. Y.Q.Q., J.X.P, and J.Z. helped perform the sample characterization. Y.L., K.Y.C., and F.Q.J. performed the DFT calculations. Y.L., F.C., Y.Q.Q., K.Y.C, F.Q.J., J.Z., and R.X. discussed the results. Y. L. and F.C. supervised the project.

The authors declare no competing financial interest.

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