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Ritu Das,1 Abhijeet Dhiman,2,3 Subodh Kumar Mishra,4 Sagarika Haldar,5,6 Neera Sharma,7 Anjali Bansal,7 Yusra Ahmad,3 Amit Kumar,4 Jaya Sivaswami Tyagi,2,5 Tarun Kumar Sharma1,5 1AptaBharat Innovation Pvt. Ltd., Faridabad, India; 2Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi, India; 3Faculty of Pharmacy, Uttarakhand Technical University (UTU), Dehradun, India; 4Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, India; 5Center for Biodesign and Diagnostics, Translational Health Science and Technology Institute, Faridabad, India; 6Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education & Research, Chandigarh, India; 7Dr Ram Manohar Lohia Hospital, New Delhi, India Background: Tuberculous meningitis (TBM) is the most devastating manifestation of extrapulmonary tuberculosis. About 33% of TBM patients die due to very late diagnosis of the disease. Conventional diagnostic methods based on signs and symptoms, cerebrospinal fluid (CSF) smear microscopy or liquid culture suffer from either poor sensitivity or long turnaround time (up to 8 weeks). Therefore, in order to manage the disease efficiently, there is an urgent and unmet need for a rapid and reliable diagnostic test. Methods: In the current study, to address the diagnostic challenge of TBM, a highly rapid and sensitive structural switching electrochemical aptasensor was developed by combining the electrochemical property of methylene blue (MB) with the molecular recognition ability of a ssDNA aptamer. To demonstrate the clinical diagnostic utility of the developed aptasensor, a blinded study was performed on 81 archived CSF specimens using differential pulse voltammetry. Results: The electrochemical aptasensor developed in the current study can detect as low as 10 pg HspX in CSF background and yields a highly discriminatory response (P