Gliomas, which originate from the glial support cells within the brain, are the most common primary intracranial tumours in adults. Primary gliomas can arise from astrocytes, oligodendrocytes, or a combination of these two types of glial cells. The most prevalent form is astrocytoma, which results from the malfunction of supporting astrocytes. These cells are crucial for maintaining neuronal homeostasis and blood-brain-barrier (BBB) function. Astrocytomas of grade IV are known as glioblastoma multiforme (GBM) and constitute the majority of malignant gliomas diagnosed in the United States. Unfortunately, GBMs pose significant challenges as they lack effective treatment options, with patients typically having a prognosis of 12-15 months following diagnosis.

Early detection of GBMs is particularly challenging because they remain entirely within the brain and are typically discovered only when symptoms such as severe headaches, convulsions, and disorientation become evident. Currently, no biomarkers have been identified that can be used for the early detection or diagnosis of GBM. The only approved methods for confirming the presence of a tumour are MRI scans and histological examinations of biopsied tissue, which are commonly employed to inform diagnosis.

These issues can be addressed by utilizing microfluidics’ capability to accurately replicate the complex microenvironmental and extracellular conditions found in the brain. Additionally, microfluidics enables the precise detection of biological phenomena with high throughput, making it a valuable tool for studying glioma progression.

Ways microfluidics help researchers better detect and understand glioblastomas

1. Early Cancer Detection of Circulating Tumour Cells (CTCs)

Firstly, microfluidics can be utilized to detect circulating tumour cells (CTCs) in patients’ biological fluids, serving as an excellent early cancer detection method. CTCs are living tumour cells that are discharged from the primary tumour into the bloodstream or lymphatic vessels, where they circulate throughout the body, potentially spreading to other organ systems. The isolation of these cells from the bloodstream provides a minimally invasive, multiple time-point liquid biopsy that can reveal a patient’s status without the need for invasive treatments.

2. Rapidly induce drug resistance in Glioblastoma

Secondly, drug resistance is one of the most serious issues in GBM treatment, as glioma stem cells develop resistance to chemotherapeutics within 48 hours after in vitro treatment. The lack of understanding of drug resistance at the molecular level is a major barrier to drug discovery. Interestingly, microfluidic devices can be utilized to rapidly induce drug resistance in GBM cell lines without requiring patient-derived tissues for resistance development research. As a result, microfluidic devices are fascinating tools for investigating possible medical treatments when site specificity is critical to drug delivery and pharmacokinetics. Furthermore, The use of a microfluidic platform in a BBB model would also enable research on the pharmacokinetics of nanoparticles as they circulate in the compromised brain delivery environment.

3. Gain mechanistic insights on tumour pathophysiology

Thirdly, the measurement of mechanical phenotypic traits, such as changes in cell structure, micromechanical cue processing, or cell-influenced extracellular matrix (ECM) remodelling, is critical for understanding tumour pathophysiology. Microfluidic cancer-on-a-chip models, therefore, facilitate the reconstruction of cancer cell microenvironments, eliminating constraints in recreating in vitro cancer systems while providing precise control over all factors. These models can perform high-resolution real-time imaging, quantify cellular response accurately, and faithfully replicate complex 3D organ-level microarchitectures. This aids in the quantification of tumour cell invasion and migration, as well as processes like intravasation, extravasation, and angiogenesis.

In conclusion, the development of organ-on-a-chip microfluidic platforms for the rapid detection of tumour-related biomarkers and the processing of tumour tissue has the potential to reduce the time between diagnosis and treatment. Therefore, continued research and development of targeted medicines, together with developments in microfluidic-based enhanced screening and detection methods, have enormous potential for improving the survival and prognosis of GBM patients.

Want to find out more about the potential of microfluidics in helping researchers and scientists further understand diseases and do better disease modelling. Check out how researchers study 4 common types of liver diseases using microfluidic devices to gain deeper insights.

References

1. Guyon J, Chapouly C, Andrique L, Bikfalvi A, Daubon T. The Normal and Brain Tumor Vasculature: Morphological and Functional Characteristics and Therapeutic Targeting. Front Physiol. 2021;12:622615. Published 2021 Mar 5. doi:10.3389/fphys.2021.622615
2. Logun M, Zhao W, Mao L, Karumbaiah L. Microfluidics in Malignant Glioma Research and Precision Medicine. Adv Biosyst. 2018;2(5):1700221. doi:10.1002/adbi.201700221