The development of a novel sensor for the detection of TB

Electronic versions

Documents

  • Mark Pitts

Abstract

Tuberculosis (TB) is an immense global problem with 8.8 million new cases, leading to an estimated 1.45 million deaths from the disease in 2010 alone. Although current serological tests have been deemed inconsistent and imprecise by the World Health Organisation, they have stated that a point of care serological test for the detection of TB would be of extreme value. This work sought to provide such a device. It was known that ELISA assays using trehalose di-mycolates, trehalose mono-mycolates and mycolic acids as antigens could be used to detect the presence of anti-TB antibodies in serum samples. It was hoped that by binding these antigens to a gold surface, the performance of the assays could be improved. Using information gained from ELISA assays, work was undertaken to develop a novel, reliable, easy to use point of care sensor for the detection of TB. It was decided to use gold nanoparticles as part of the sensor, and thiol modified antigens, as well as non-thiol modified antigens (via a linker compound) were successfully bound to their surfaces. It was discovered that addition of a sodium chloride solution to the antigen coated gold nanoparticles led to their aggregation, in tum, changing the colour of the solution from red to blue. It was also discovered that this process could be inhibited by the addition of a TB positive serum sample to the coated gold nanoparticles prior to adding the sodium chloride solution. These observations were used to develop a novel assay for the detection of TB, which could be performed in as little as 15 minutes. Large numbers of serum samples from high burden TB populations were analysed by the developed assay, and although a number of false positive samples were detected, largely from patients with a record of infection with malaria, almost all of the positive samples could be detected with multiple antigens. The assay developed was then incorporated into a device which is fully portable and easy to use, and can be read by eye, by observing the colour of the coated gold nanoparticle solution, and potentially, by measuring its absorbance at two different wavelengths.

Details

Original languageEnglish
Awarding Institution
  • Bangor University
Supervisors/Advisors
  • Mark Baird (Supervisor)
  • Christopher Gwenin (Supervisor)
Award dateJul 2013