Project Lead(s): Edmond Young
Tuberculosis (TB) is a fatal infectious disease and a major ongoing global health challenge.
It is the second leading infectious disease killer after HIV, with 8.7 million incident cases and 1.4 million deaths from TB reported in 2011.
Compounding the problem is the growing prevalence of TB with multi-drug resistance (MDR) and extensive-drug resistance (XDR).
The most common TB diagnostic methods are sputum smear microscopy, which lacks sensitivity, and liquid broth culture, which is sensitive but time-consuming and requires infrastructure.
The primary objective of this project was to develop a novel assay that can detect tuberculosis (TB) drug susceptibility in sputum samples obtained directly from patients and assess resistance to many drugs at once.
If developed, the assay kit could be used on the front line of clinical diagnostics, where healthcare workers could easily ‘snap together’ different parts of the designed kit and obtain drug susceptibility data for that specific patient within 24 hours – more rapid than any other TB culture system currently in use (not including gene-based tests like GeneXpert).
The key achievement to date was the complete design, fabrication and drug-based characterization of the proposed MDR-TB microfluidic cell culture assay, with validation that the system functions as proposed, to provide a 24-hour readout of drug susceptibility in the form of bacteria cell viability dose-response curves.
The team managed to fabricate more than 100 prototypes, using more than 50 of the devices for experimental testing and drug characterization, and delivering 50 more of the devices to Thailand for testing in the labs at Mahidol University and Siriraj Hospital in Bangkok, Thailand.
They developed an assay protocol specifically for use with the microfluidic chip, including unique TB cell capture via magnetic micro beads conjugated to a lectin, and tested the drug susceptibility for four major bacteria cell line models (M. smegmatis, M.marinum, M. H37Ra, M. chromogenicum) exposed to four major TB drugs currently in use (rifampicin, isoniazid, ethambutol and kanamycin).
The project has received funding from two Engage Grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) of $25,000 each (total $50,000); the Ontario Centres of Excellence VIP Program ($25,000) and a Mitacs Accelerate Fellowship ($15,000).
The team plans on applying for Phase II Transition To Scale funding as soon as they have obtained sufficient preliminary data from the clinical trial to prove the validity and clinical utility of the platform.