Acute respiratory tract infections (ARTIs) are a global health concern, affecting millions annually. The challenges in accurately and rapidly diagnosing these infections are immense, given their diverse causative agents and overlapping symptoms. Microfluidic technologies, however, are emerging as a revolutionary solution, promising to transform the landscape of ARTI diagnosis.
Fig.1 Schematic illustration of the diagnosis triad for infections of the respiratory tract. (Liu K. Z., et al., 2025)
The Burden of Acute Respiratory Tract Infections
ARTIs encompass a wide range of diseases, from the common cold to life-threatening pneumonia. Seasonal influenza alone causes 3 to 5 million severe cases and about 290,000 to 650,000 respiratory deaths globally each year, according to the World Health Organization. The 2003 Severe Acute Respiratory Syndrome (SARS) outbreak, with a mortality rate of around 10%, and the ongoing COVID-19 pandemic, which has infected hundreds of millions worldwide, highlight the devastating potential of respiratory infections.
These infections not only impact public health but also strain healthcare systems and economies. The costs associated with hospitalization, treatment, and lost productivity are staggering. For example, during the H1N1 influenza pandemic in 2009, the economic impact was estimated to be in the billions of dollars globally.
Limitations of Traditional Diagnostic Methods
Traditional diagnostic methods for ARTIs have significant drawbacks. Microbial culture, once the gold standard, can take days to weeks to grow and identify pathogens. This delay is critical, as it can lead to inappropriate treatment and the spread of infections. Serological tests, which detect antibodies in the blood, are often unable to distinguish between current and past infections, and they may not be sensitive enough in the early stages of disease.
Nucleic acid amplification tests (NAATs), such as polymerase chain reaction (PCR), are more accurate but require sophisticated laboratory equipment, trained personnel, and relatively long processing times. In resource-limited settings, these requirements can be a major barrier to timely diagnosis.
How Microfluidics Works
Microfluidics involves the manipulation of small volumes of fluids, typically in the microliter to picoliter range, within microchannels. These channels, often fabricated on a chip, can be designed to perform a variety of functions, from sample preparation to detection.
Centrifugal Microfluidics
Centrifugal microfluidics, or "lab - on - a - disk" systems, use rotational forces to move fluids through channels on a spinning disk. This method allows for precise control of fluid flow and can be used to perform multiple steps in an assay, such as sample lysis, nucleic acid extraction, and amplification. For example, a centrifugal microfluidic device developed for influenza detection can process a sample and provide results within 30 minutes, much faster than traditional methods.
Pressure-Driven Microfluidics
Pressure-driven microfluidics uses external pressure sources, such as pumps or compressed air, to push fluids through channels. This approach can achieve high-speed and high-precision fluid delivery. In some cases, pneumatic valves can be integrated into the system to control the flow of fluids, enabling complex assay protocols. A pressure - driven microfluidic device for SARS - CoV - 2 detection demonstrated high sensitivity and specificity, with results available in less than an hour.
Digital Microfluidics
Digital microfluidics manipulates individual droplets of fluids, rather than continuous streams. This is often achieved using techniques like electrowetting - on - dielectric, where an electric field is used to move droplets across a hydrophobic surface. Digital microfluidics allows for precise control of small volumes, which is useful for applications such as droplet digital PCR. In the context of ARTIs, digital microfluidic devices can perform highly sensitive nucleic acid quantification, enabling the detection of low-level infections.
Capillary and Paper-Based Microfluidics
Capillary microfluidics relies on capillary forces to move fluids through narrow channels. This self-contained and passive approach requires no external pumps, making it simple and cost-effective. Paper-based microfluidics, a subset of capillary microfluidics, uses porous paper as the substrate. These devices can be easily fabricated and are highly portable. For instance, a paper-based microfluidic test strip for respiratory syncytial virus (RSV) detection can provide visual results within 15 minutes, suitable for use in resource-limited settings.
Microfluidics in ARTI Diagnosis: Applications
Microfluidic technologies are being applied in various aspects of ARTI diagnosis.
One of the major advantages of microfluidics is the ability to perform multiplex detection, simultaneously identifying multiple pathogens in a single sample. For example, a microfluidic chip can be designed to detect influenza A and B viruses, RSV, and adenovirus all at once. This is crucial as co-infections are common in respiratory diseases, and accurate identification of all causative agents is necessary for effective treatment.
Microfluidic devices are well-suited for point-of-care (POC) testing, which can provide immediate results at the patient's bedside or in a community setting. POC microfluidic tests for ARTIs can eliminate the need for sample transport to a central laboratory, reducing turnaround time and improving patient care. A handheld microfluidic device for COVID-19 antigen detection can give results in as little as 10 minutes, enabling rapid triage and isolation of infected individuals.
Microfluidics can also simplify and automate sample preparation steps, such as nucleic acid extraction and purification. By integrating these steps on-chip, microfluidic devices can reduce the risk of contamination and improve the efficiency of the diagnostic process. For example, a microfluidic system can extract and purify viral nucleic acids from a nasal swab sample in a single, automated process, ready for subsequent detection.
Commercial and Research Developments
In the commercial realm, several companies are developing and marketing microfluidic-based diagnostic products for ARTIs. For example, some companies offer PCR-based microfluidic platforms that can detect a panel of respiratory pathogens in a short time. These devices are being used in hospitals and clinics to improve diagnostic accuracy and speed.
In research, scientists are constantly exploring new applications of microfluidics in ARTI diagnosis. This includes the development of new detection methods, such as integrating CRISPR-Cas technology with microfluidics for highly specific pathogen identification. Additionally, efforts are underway to improve the sensitivity and specificity of microfluidic devices, as well as to reduce their cost for wider adoption.
Challenges and Future Outlook
Despite the great potential of microfluidics in ARTI diagnosis, there are challenges to overcome. Regulatory approval processes for new microfluidic diagnostic devices can be complex and time-consuming. Ensuring the long-term stability of reagents in microfluidic systems, especially in resource-limited settings with variable storage conditions, is also a concern.
Looking to the future, microfluidics is expected to play an even more significant role in ARTI diagnosis. Advancements in materials science, nanotechnology, and sensor technology will likely lead to more sensitive, specific, and user-friendly microfluidic devices. The integration of artificial intelligence and machine learning with microfluidics may further enhance diagnostic accuracy and data analysis, revolutionizing the way we detect and manage acute respiratory tract infections.
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Reference
- Liu, Kan-Zhi, et al. "Microfluidic methods for the diagnosis of acute respiratory tract infections." Analyst 150.1 (2025): 9-33.
This article is for research use only. Do not use in any diagnostic or therapeutic application.
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