Lab-on-Chip-Based Platform for Fast Molecular Diagnosis of Multidrug-Resistant Tuberculosis

Abstract

hWe evaluated the performance of the molecular lab-on-chip-based VerePLEX Biosystem for detection of multidrug-resistant tuberculosis (MDR-TB), obtaining a diagnostic accuracy of more than 97.8% compared to sequencing and MTBDRplus assay for Mycobacterium tuberculosis complex and rifampin and isoniazid resistance detection on clinical isolates and smear-positive specimens. The speed, user-friendly interface, and versatility make it suitable for routine laboratory use. Multidrug-resistant tuberculosis (MDR-TB) requires long and expensive treatment and often results in poor clinical outcome in both low-and high-income countries (1, 2). The World Health Organization (WHO) has endorsed specific molecular diagnostics to improve fast diagnosis of MDR-TB (3-5).However, the genotypic diversity and geographical distribution of Mycobacterium tuberculosis complex (MTBC), together with the inability to provide appropriate interpretation of silent mutations and the limited versatility are some of the restraints undermining the effectiveness of the current tools on a global scale (6-13).In the present study, we evaluated a lab-on-chip (LoC) device, developed by STMicroelectronics (Geneva, Switzerland) and marketed by Veredus Laboratories (Republic of Singapore) as the VerePLEX Biosystem, for the diagnosis of MDR-TB and detection of common nontuberculous mycobacteria (NTM). The molecular assay was evaluated on both clinical isolates and direct specimens in low-and high-burden settings.We tested 91 MTBC isolates (see Table S1 in the supplemental material) harboring different patterns of mutations in rpoB, katG, and inhA genes to evaluate the probes on the array listed in Table 1. Eighty respiratory specimens positive for acid-fast bacilli by smear microscopy and MTBC culture positive were decontaminated according to international guidelines and included in the study (Table S1) (14). An additional 116 MTBC culture-negative specimens were included in the analysis. DNA from isolates and specimens was extracted by thermal lysis and sonication as described elsewhere (15). Phenotypic drug susceptibility testing (DST) for rifampin (RIF) and isoniazid (INH) was performed according to international recommendations (16). Some of the

Application of nanodiagnostics in point-of-care tests for infectious diseases

“…Among them, lab-on-a-chip and microfluidics techniques have shown good promise for the detection of infectious diseases. 54,55 Through these techniques, multiple assays could be integrated into one single device, 56,57 resulting in a decrease in the volume of samples from infected patients, the consumption of materials, and the analysis time. These advantages of the integrated systems could greatly potentiate to build low-cost and portable devices.…”

Diagnostic tools for tackling febrile illness and enhancing patient management

“…The cost per VereTrop™ test is approximately US$100. Sample preparation is performed ex situ, either via spin columns or an automated extraction kit, and the overall time-to-result (including extraction, amplification, optical readout) adds up to approximately 3.5 h. VereFlu™ [115] and VereTrop™ [116] assay chips and multi drug resistant tuberculosis [117] have been clinically validated.…”

Lab-on-Chip Technology: A Review on Design Trends and Future Scope in Biomedical Applications

“…The effectiveness of current methods is restricted by limited versatility, inappropriate interpretation of silent mutations and the geographical distribution and genotypic diversity of Mycobacterium tuberculosis complex (MTBC). To overcome all these challenges, STMicroelectronics (Geneva, Switzerland) has developed a Lab-on-Chip device known as VerePLEX Biosystem [26]. This molecular LoC based system has the potential to diagnose the MDR-TB considering time constraint and to rapidly detect the common Nontuberculous Mycobacteria (NTM) so as to reduce the mortality and morbidity rate.…”