A paper-based test for tuberculosis diagnosis in developing countries

Scientists from Taiwan have developed a “paper” test for the diagnosis of tuberculosis infection
   Early diagnosis of tuberculosis (TB) allows patients to receive proper treatment and helps prevent the disease from spreading. However, in resource-limited areas, expensive test equipment and long wait times for results are obstacles to TB diagnosis and treatment. To overcome this problem, scientists report in ACS Sensors the development of a fast paper-based tuberculosis test that can be read with a smartphone.
   The World Health Organization reported that in 2015, 1.4 million people died from TB, with most of these deaths occurring in low- and middle-income countries. Early diagnosis could help decrease these numbers. However, conventional methods such as sputum smear microscopy, immunological methods, molecular tests, culture-based techniques, and those involving the use of chest X-rays and CT scans require equipment, electricity and well-trained personnel, which are not always available in remote or developing areas. Thus, Professor Chien-Fu Chen from National Taiwan University and colleagues sought to devise a more practical diagnostic test that can be read with a smartphone, a technology that is increasingly available in emerging economies (Figure 1).
Figure 1. TB diagnosis in central clinics and the proposed on-site test with a paper-based detection system.
   The researchers developed a colorimetric sensing strategy employing gold nanoparticles and a paper-based analytical platform for the diagnosis of TB (Figure 2). Through the use of the surface plasmon resonance effect, the changes in the color of a gold nanoparticle colloid induced by the hybridization of single-stranded DNA probe molecules with target double-stranded TB DNA from Mycobacterium tuberculosis, the bacteria that cause TB, can be monitored. The hybridization event changes the surface charge density of the nanoparticles, causing them to aggregate to various degrees, which alters the color of the solution in a manner that can be readily measured to determine the concentration of the target DNA analyte. In the presence of the target TB DNA sequences, the hybridization of these sequences and specific designed DNA probe causes the distance between neighboring gold nanoparticles in a salt solution to decrease, so the surface plasmon resonance of the material redshifts, causing the color of the suspension to change from wine red to blue. The color change in the AuNP mixture provides a practical platform for absorption-based colorimetric sensing of a target analyte that directly or indirectly triggers AuNP aggregation or redispersion.
Figure 2. The colorimetric TB diagnostic strategy.
   To adapt this TB diagnosis method to resource-limited settings, a label-free oligonucleotide-modified and unmodified gold nanoparticle solution-based technique was incorporated with a paper-based device that could be easily disseminated and used throughout the developing world. The resulting gold nanoparticle-DNA colloid can be spotted onto the paper device and then measured using a smartphone for sample detection, enabling the realization of rapid on-site quantitative and parallel analysis and providing a simple means of data storage via cloud computing, which means that minimal equipment is required. A tissue sample from an infected patient was tested to further demonstrate that the device could be used in the field. Therefore, with only a smartphone, this paper TB test was able to rapidly measure parallel colorimetric results, eliminating the need for expensive reagents or sophisticated analytical instruments. Accordingly, this sensitive diagnostic test could have practical value around the world.
   This study has been highlighted and reported by the American Association for the Advancement of Science (AAAS), the American Chemical Society (ACS), IEEE GlobalSpec, and the Russian News Agency (TASS).
Tsai, T., Huang, C., Chen, C., Shen, S., Wang, M., Cheng, C., and Chen, C. (2017). Diagnosis of Tuberculosis Using Colorimetric Gold Nanoparticles on a Paper-Based Analytical Device. ACS Sensors, 2(9), 1345 - 1354. DOI:10.1021/acssensors.7b00450
Chien-Fu Chen
Assistant Professor, Institute of Applied Mechanics