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Detection of BCG bacteria using a magnetoresistive biosensor: A step towards a fully electronic platform for tuberculosis point-of-care detection
Biosensors and Bioelectronics ( IF 10.7 ) Pub Date : 2017-09-06 , DOI: 10.1016/j.bios.2017.09.004
Teresa G. Barroso , Rui C. Martins , Elisabete Fernandes , Susana Cardoso , José Rivas , Paulo P. Freitas

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 104 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 0.03 log10 (cells/mL). Results show that Ziehl-Neelsen detection limits and below are achievable with the magnetoresistive biochip, when pre-processing and chemometrics are used.



中文翻译:

使用磁阻生物传感器检测BCG细菌:迈向结核病即时诊断全电子平台的一步

结核病是主要的公共卫生问题之一。这种高度传染性疾病影响了超过1,040万人,是感染导致发病的主要原因。Ziehl-Neelsen痰涂片显微镜检查可在医护点诊断出结核病。Ziehl-Neelsen费力,容易出现人为错误和感染风险,检出限为10 4细胞/ mL。在资源匮乏的国家具有较低检测限的更实用的测试至关重要。这项工作使用磁阻生物传感器来检测BCG细菌以进行结核病诊断。我们在此报告:i)纳米颗粒组装方法和结核病检测的特异性;ii)证明BCG细胞浓度与磁阻电压信号之间的比例关系;iii)乘性信号校正在系统效果消除中的应用;iv)使用化学计量学方法研究校准有效性;v)与最新的即时护理结核病生物传感器进行比较。

结果表明电压信号与细胞浓度之间存在明显的对应关系。乘法信号校正消除了生物芯片传感器内部和之间的基线偏移,从而允许不同生物芯片之间的电压信号精确而精确。校正后的信号用于多元回归模型,从而将校准标准误从0.50降低到0.03 log 10(细胞/ mL)。结果表明,使用预处理和化学计量学时,磁阻生物芯片可以达到Ziehl-Neelsen的检出限及以下检出限。

更新日期:2017-09-06
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