Recent advances in biosensing technologies have leveraged the unique properties of two-dimensional materials for real-time biomarker detection. Among these materials, MXenes, particularly Ti3C2Tx, have emerged as a promising platform for impedance-based biosensors due to their exceptional electrical conductivity, tunable surface chemistry, and biocompatibility. These attributes make them highly suitable for monitoring cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which are critical indicators of inflammatory responses in conditions like sepsis and COVID-19 cytokine storms.

MXenes are a class of transition metal carbides, nitrides, and carbonitrides with a layered structure. Ti3C2Tx, the most studied MXene, is synthesized by selectively etching the aluminum layer from Ti3AlC2 (MAX phase) using hydrofluoric acid or fluoride-containing solutions. The resulting material possesses a high density of surface-terminating functional groups (-O, -F, -OH), denoted by Tx, which can be further modified to enhance biomolecule immobilization. The metallic conductivity of MXenes, often exceeding 10,000 S/cm, enables highly sensitive electrochemical impedance spectroscopy (EIS) measurements, where even minor changes in surface charge or mass due to biomarker binding can be detected.

The performance of MXene-based impedance biosensors relies on the efficient immobilization of antibodies or aptamers on the material’s surface. The presence of oxygen-containing groups on Ti3C2Tx allows covalent conjugation strategies, such as carbodiimide chemistry (EDC/NHS), to link antibodies via amine groups. Alternatively, physical adsorption or electrostatic interactions can be employed, taking advantage of MXene’s negatively charged surface. The high surface area of MXenes ensures a dense packing of biorecognition elements, improving sensor sensitivity. Studies have demonstrated that MXene-functionalized electrodes achieve detection limits in the picogram per milliliter range for cytokines, outperforming conventional gold or carbon-based electrodes.

One of the most significant advantages of MXene-enabled biosensors is their rapid response time. Traditional enzyme-linked immunosorbent assays (ELISA) require several hours due to multiple incubation and washing steps, whereas MXene-based impedance sensors provide real-time measurements within minutes. This rapid detection is crucial for clinical applications such as sepsis management, where early intervention is critical. Elevated levels of IL-6 and TNF-α are early indicators of systemic inflammation, and continuous monitoring can guide timely therapeutic decisions. Similarly, in COVID-19 patients, the ability to track cytokine storms in real time can prevent severe outcomes by enabling prompt immunosuppressive treatment.

A major challenge in biosensing is fouling caused by nonspecific protein adsorption in complex biofluids like serum or whole blood. MXenes offer several strategies to mitigate fouling. Surface passivation with polyethylene glycol (PEG) or zwitterionic polymers reduces nonspecific binding while maintaining antibody accessibility. Additionally, the hydrophilicity of MXenes, attributed to their functional groups, minimizes hydrophobic interactions with proteins. Some studies have also explored the use of MXene-polymer composites, where the polymer matrix further enhances antifouling properties without compromising conductivity.

The stability of MXenes in aqueous environments is another consideration. While Ti3C2Tx is prone to oxidation over time, encapsulation with inert materials or storage in oxygen-free conditions can prolong its functionality. Recent developments in MXene-polymer hybrids have improved both stability and mechanical robustness, making them suitable for long-term biosensing applications.

Beyond cytokine monitoring, MXene-based biosensors hold potential for multiplexed detection. By patterning multiple electrodes with different antibodies, simultaneous measurement of several biomarkers can be achieved. This capability is particularly valuable in sepsis and COVID-19, where multiple cytokines contribute to disease progression. Furthermore, the integration of MXene sensors with wearable or point-of-care devices could enable decentralized monitoring, reducing reliance on centralized laboratories.

In summary, MXene-enabled impedance biosensors represent a significant advancement in real-time cytokine detection. Their high conductivity, tunable surface chemistry, and rapid response times address key limitations of traditional assays like ELISA. With further optimization in antifouling strategies and long-term stability, these sensors could revolutionize the management of inflammatory conditions, providing clinicians with timely and actionable data. The ongoing development of MXene-based platforms underscores their potential not only in diagnostics but also in personalized medicine, where continuous biomarker tracking can inform tailored therapeutic interventions.

The future of MXene biosensors lies in scaling up production while maintaining consistency in material properties. Advances in inkjet printing or roll-to-roll manufacturing could facilitate large-scale deployment. Additionally, combining MXenes with machine learning algorithms for data analysis could enhance the predictive power of these sensors, enabling early warning systems for cytokine storms or sepsis onset. As research progresses, the translation of MXene biosensors from laboratory prototypes to clinical tools will depend on rigorous validation in real-world settings, ensuring reliability across diverse patient populations.

The intersection of nanomaterials and biosensing continues to push the boundaries of medical diagnostics, and MXenes are at the forefront of this innovation. Their unique properties position them as a versatile platform not only for cytokine monitoring but also for a wide range of biomedical applications, from infectious disease detection to cancer biomarker screening. As the field evolves, the integration of MXenes into next-generation diagnostic devices promises to deliver faster, more accurate, and more accessible healthcare solutions.