MICROFLUIDICS FOR THE DIAGNOSIS AND TREATMENT OF TUBERCULOSIS
What is Tuberculosis (TB)?
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis. It primarily affects the lungs but can also spread to other parts of the body, such as the brain, kidneys, and spine. TB is one of the top infectious disease killers worldwide, particularly affecting low-income and developing regions.
Tuberculosis and Microfluidics
The emergence of microfluidic technologies represents a significant advancement in the diagnosis and treatment of tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (M. tuberculosis or Koch’s bacillus).
Accurate and rapid detection of this pathogen is crucial for effective disease management, as timely diagnosis can lead to appropriate quarantine and treatment measures. Recent innovations in integrated microfluidic systems have shown promise in enhancing the capture, enrichment, and analysis of M. tuberculosis, addressing the complex challenges associated with TB diagnosis and therapy.
In addition to diagnosis, microfluidics has also transformed the landscape of drug susceptibility testing for TB, particularly in the context of drug-resistant strains. By incorporating microfluidic devices into TB research, scientists have gained deeper insights into bacterial behavior and drug interactions, significantly improving disease management strategies. The urgent need for innovative methodologies to tackle the persistent nature of the pathogen has further emphasized the importance of microfluidic technologies.
Microfluidics for Rapid Drug Susceptibility Testing in Tuberculosis
Microfluidics has emerged as a transformative technology in the field of tuberculosis (TB) diagnosis and treatment, particularly in addressing the challenges posed by drug-resistant strains. The incorporation of microfluidic devices into TB research enhances our understanding of bacterial behavior and drug interactions, providing significant improvements in the management of the disease.
The development of microfluidic chips allows for precise control over microenvironmental conditions, enabling the trapping of bacteria in microchambers where behaviors can be closely monitored. A notable advancement involves the simultaneous tracking of single-cell growth, both with and without antibiotic exposure. By employing a deep neural network image-segmentation algorithm, researchers quantified bacterial growth rates over time and analyzed the responses of various strains to antibiotic treatments in comparison to untreated controls [1]. This level of detail enables researchers to assess the effectiveness of drugs on a per-cell basis, offering insights into the dynamics of drug susceptibility and resistance.
Furthermore, the increasing prevalence of drug-resistant tuberculosis strains necessitates innovative approaches to diagnosis and treatment. Traditional methods have often fallen short in providing the timely and accurate information required for effective patient management [2]. Microfluidic devices bridge this gap by offering capabilities that enhance treatment prescription, thus advancing knowledge about the disease and its interactions within the human body. These devices can streamline the process of identifying effective antibiotics, making it possible to tailor treatment plans based on individual patient needs and bacterial strain behavior.
Overall, the integration of microfluidics into tuberculosis research represents a significant advancement in rapid drug susceptibility testing. The ability to monitor single-cell responses to antibiotics offers unprecedented insights into bacterial behavior and resistance mechanisms.
Microfluidic Systems for Detection and Characterization of Mycobacterium tuberculosis
Accurate and rapid detection of M. tuberculosis is crucial for effective disease management, as timely diagnosis can facilitate appropriate quarantine and treatment measures. Recently, integrated microfluidic systems have been explored for their ability to enhance the capture, enrichment, and analysis of this pathogen, providing a promising avenue for tackling the challenges associated with TB diagnosis and therapy. [3]
Airborne capture associated to bacterial immunoassay
A notable innovation in the field is the development of an integrated microfluidic system designed specifically for the airborne capture and rapid bacteriological immunoassay of M. tuberculosis. This system addresses a critical limitation in pathogen detection, particularly the low concentration of pathogens present in air samples, which hampers rapid analysis and timely diagnosis [4]. The total detection process was reduced to under 50 minutes, comprising 20 minutes for enrichment and 30 minutes for immunoreaction analysis. By enhancing the capture efficiency of airborne bacteria, this technology paves the way for more effective surveillance and monitoring of TB cases in environments where transmission risk is heightened.
Cleaned-up samples for genomic analysis
Moreover, research has demonstrated the efficacy of microfluidic lab-on-chip platforms for clean-up and pathogen concentration from clinical samples. In a proof-of-principle study, the Capture-XT microfluidic system showed promising results in enriching M. tuberculosis bacilli from sputum specimens (lung mucus). Notably, the study revealed that 75% of the processed samples passed the library preparation quality control for downstream DNA extraction and whole-genome sequencing (WGS), compared to only 25% of the unprocessed samples. This indicates the potential of microfluidic techniques to enhance the quality of genomic analyses for pathogen characterization, offering more reliable insights into TB strains and their resistance profiles [5].
Tuberculosis Microreactors
Advancements in microfluidic systems extend beyond detection to treatment, particularly antibiotic efficacy. A bioengineered cell culture platform replicates key features of human disease by integrating primary human cells, a 3D structure, virulent bacteria, and pharmacokinetic modeling. This microsphere system allows precise control over cell content, extracellular matrix, sphere size, and infectious dose, making it adaptable for studying various infections.
For TB treatment, this platform simulated 3D culture conditions to test pyrazinamide, a first-line antibiotic. M. tuberculosis showed sensitivity in microspheres but not in 2D cultures, highlighting the system’s ability to mimic in vivo environments and improve therapeutic insights, including antimicrobial resistance [6].
Ultimately, the progress in microfluidics for the detection and treatment of M. tuberculosis illustrates the transformative potential of this technology in public health. By enhancing the detection capabilities, improving pathogen characterization, and creating more relevant models for antibiotic testing, these innovative systems address key challenges in TB management. The integration of microfluidic platforms could ultimately lead to more effective control strategies and reduced transmission rates of tuberculosis globally [7].
The best for your flow controlled experiment
Advances and Limitations in Microfluidics for Tuberculosis (TB) Diagnosis and Treatment
Recent advancements in microfluidics for TB detection and treatment represent a major leap forward in public health. These innovations enhance diagnostic accuracy, improve pathogen characterization, and refine antibiotic testing models.
Key Advances in Microfluidic TB Research:
- Enhanced Detection and Characterization
- Microfluidic systems improve the detection of Mycobacterium tuberculosis.
- Advanced characterization techniques allow for better pathogen profiling and antibiotic testing.
- Rapid Drug Susceptibility Testing
- Single-cell analysis enables real-time monitoring of bacterial responses to antibiotics.
- Helps combat antibiotic resistance, a growing global health concern.
- High-Throughput Screening & Single-Cell Analysis
- Microfluidic technology supports faster, more efficient TB testing.
- Allows the development of realistic in vitro models to mimic infection scenarios.
Such advancements promote thorough understanding and management of this significant public health challenge. Despite these notable advancements, limitations persist. Challenges include the integration of microfluidic systems into existing public health frameworks, ensuring widespread accessibility and affordability of these technologies, and navigating regulatory pathways. Furthermore, there is a need for ongoing research to explore the full potential of these technologies in various clinical settings. The most promising directions for future research and innovation in this field involve enhancing the sensitivity and specificity of microfluidic devices, exploring new antibiotic testing methods, and developing robust models that accurately mimic human infection scenarios. Emphasizing collaboration between researchers, clinicians, and public health officials will be crucial to translate these advances into effective solutions for TB diagnosis and treatment on a global scale.
Advanced Microfluidic range
Written and reviewed by Louise Fournier, PhD in Chemistry and Biology Interface, For more content about microfluidics, you can have a look here.
References
[1] B. M. Tran, J. Larsson, A. Grip, P. Karempudi, and J. Elf, “One-day phenotypic drug susceptibility testing for mycobacterium tuberculosis variant bovis BCG using single-cell imaging and a deep neural network.” May 2024. Available: [‘http://dx.doi.org/10.1101/2024.05.20.594971’, ‘https://syndication.highwire.org/content/doi/10.1101/2024.05.20.594971’]
[2] M. Cañadas-Ortega, C. Gómez-Cruz, J. J. Vaquero, and A. Muñoz-Barrutia, “The contribution of microfluidics to the fight against tuberculosis,” [’Nanotechnology Reviews’], vol. 11, pp. 40–54, Dec. 2021, doi: 10.1515/ntrev-2022-0004.
[3] C.-H. Wang, J.-R. Chang, S.-C. Hung, H.-Y. Dou, and G.-B. Lee, “Rapid molecular diagnosis of live mycobacterium tuberculosis on an integrated microfluidic system,” [’Sensors and Actuators B: Chemical’], vol. 365, p. 131968, Aug. 2022, doi: 10.1016/j.snb.2022.131968.
[4] W. Jing, X. Jiang, W. Zhao, S. Liu, X. Cheng, and G. Sui, “Microfluidic platform for direct capture and analysis of airborne <i>mycobacterium tuberculosis</i>,” [’Analytical Chemistry’], vol. 86, pp. 5815–5821, May 2014, doi: 10.1021/ac500578h.
[5] N. Ismail et al., “Microfluidic capture of mycobacterium tuberculosis from clinical samples for culture-free whole-genome sequencing,” [’Microbiology Spectrum’], Jun. 2023, doi: 10.1128/spectrum.01114-23.
[6] M. K. Bielecka et al., “A bioengineered three-dimensional cell culture platform integrated with microfluidics to address antimicrobial resistance in tuberculosis,” [’mBio’], vol. 8, Mar. 2017, doi: 10.1128/mbio.02073-16.
[7] A. Molloy et al., “Microfluidics as a novel technique for tuberculosis: From di-agnostics to drug discovery.” Sep. 2021. Available: [‘http://dx.doi.org/10.20944/preprints202109.0491.v1’]
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