Microfluidic and MEMS-Based Biosensing Platforms for Fungal Respiratory Infections in Immunocompromised Patients: Toward Rapid, Specific, and Minimally Invasive Diagnosis

Invasive fungal respiratory infections (IFRIs) remain a major cause of morbidity and mortality among immunocompromised patients, yet diagnosis continues to be hindered by nonspecific clinical features, limited sample accessibility, and the poor sensitivity or specificity of conventional tests. Microfluidic and microelectromechanical systems (MEMS)-based biosensing platforms have emerged as promising alternatives, enabling rapid, minimally invasive, and highly specific detection of fungal pathogens and host responses. Microfluidic nucleic acid and antigen assays allow on-chip amplification and immunodetection with reduced sample volumes and turnaround times, while CRISPR-enhanced systems further improve analytical sensitivity. Parallel advances in host-response profiling—including transcriptomic, proteomic, and cytokine-based signatures—have demonstrated feasibility for integration into lab-on-a-chip platforms. MEMS-based technologies extend this potential by facilitating real-time analysis of exhaled volatile organic compounds, mechanical biosensing of fungal DNA and antigens, and in situ monitoring of device-associated biofilms. Translational studies highlight potential applications across intensive care, hematology–oncology, and transplant settings, as well as in outpatient monitoring of high-risk populations. However, several challenges remain, including limited multicenter validation, matrix-related biofouling effects, and lack of standardization in fungal biomarker panels. Future directions include AI-driven interpretation of multianalyte data, multiplexed integration of host and pathogen markers, and development of fully cartridge-based systems for near-patient deployment. Collectively, these innovations may shift fungal diagnostics toward earlier, more precise, and patient-tailored interventions, improving outcomes in vulnerable populations.