Tuberculosis is one of the major public health concerns. This highly contagious disease affects more than 10.4 million people, being a leading cause of morbidity by infection. Tuberculosis is diagnosed at the point-of-care by the Ziehl-Neelsen sputum smear microscopy test. Ziehl-Neelsen is laborious, prone to human error and infection risk, with a limit of detection of 10 cells/mL. In resource-poor nations, a more practical test, with lower detection limit, is paramount. This work uses a magnetoresistive biosensor to detect BCG bacteria for tuberculosis diagnosis. Herein we report: i) nanoparticle assembly method and specificity for tuberculosis detection; ii) demonstration of proportionality between BCG cell concentration and magnetoresistive voltage signal; iii) application of multiplicative signal correction for systematic effects removal; iv) investigation of calibration effectiveness using chemometrics methods; and v) comparison with state-of-the-art point-of-care tuberculosis biosensors. Results present a clear correspondence between voltage signal and cell concentration. Multiplicative signal correction removes baseline shifts within and between biochip sensors, allowing accurate and precise voltage signal between different biochips. The corrected signal was used for multivariate regression models, which significantly decreased the calibration standard error from 0.50 to 0.03log (cells/mL). Results show that Ziehl-Neelsen detection limits and below are achievable with the magnetoresistive biochip, when pre-processing and chemometrics are used.

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Tuberculosis is still a major global health concern, causing the estimated death of 1.5 million people per year and being associated with high morbidity. The development of point-of-care diagnostic tools for tuberculosis is mandatory, especially because the fast and accurate detection of the slow-growing Mycobacterium tuberculosis by the conventional diagnostic tests is difficult.The objective of this work was to develop the first steps to achieve a portable method for the diagnosis of tuberculosis, by a sandwich-immunoassay combined with magnetoresistive biochip technology.With the purpose of conjugating 250 nm streptavidin-coated magnetic nanoparticles with anti- M.tuberculosis biotinylated antibodies, Mycobacteriumbovis Bacillus Calmette-Guérin was used as a surrogate for M. tuberculosis bacteria. After magnetic capture, target bacteria were brought in contact with the surface of the magnetoresistive biochip previously functionalized with a secondary anti-M.tuberculosis antibody. Magnetically labeled cells were detected by an array of spin-valve sensors, which change their electrical resistance in the presence of the fringe field of the magnetic particles. Optimization studies on the efficiency of the magnetic capture and further recognition of the bacteria by the secondary antibody on the biochip surface were conducted. The results on the magnetoresistive biochip showed a clear difference in the signal between specific and control (non-specific) sensors, suggesting the usefulness of this technique as a potential biorecognition tool for the development of a point-of-care diagnostic method for tuberculosis.