Tiny vortexes help detect dangerous viruses

Saliva-based diagnostics have emerged as a transformative approach in medical testing, offering a non-invasive and efficient alternative to blood sampling. However, the complexity of saliva, which contains a mix of cells, bacteria, and large microvesicles, has posed challenges in isolating biomarkers critical for accurate diagnostics.

Addressing this, researchers at Duke University have developed an innovative acoustofluidic integrated molecular diagnostics (AIMDx) chip. Published in Science Advances, this breakthrough combines purification and detection functionalities, streamlining the process of identifying key viral and immune markers.

The AIMDx chip employs a series of acoustically oscillating wedge microstructures within a polydimethylsiloxane (PDMS) microfluidic channel. These wedges generate acoustic streaming vortices that enable the precise separation of biological components.

When saliva samples are introduced, larger particles, such as cells and microvesicles, are trapped in the vortex centers, while smaller particles, including antibodies and viruses, flow downstream.

This mechanism, driven by subwavelength Gor’kov potential wells, ensures high precision in separating particles as small as 200 nm. Experimental demonstrations revealed that particles larger than 1 μm were effectively removed, leaving a purified sample rich in antibodies and viruses.

Notably, this purification method preserves critical biomarkers, enhancing the sensitivity of downstream analyses. Furthermore, the use of low-frequency acoustic chips eliminates the need for bulky radio-frequency power amplifiers, making the technology compact and suitable for point-of-care applications.

The significance of this innovation lies in its ability to address a persistent issue in diagnostic testing: the presence of large contaminants in samples. Traditional methods such as centrifugation and filtration can inadvertently remove vital biomarkers, reducing the accuracy of diagnostic results. The AIMDx chip’s acoustic purification method circumvents this problem, ensuring that essential particles remain intact for subsequent analysis.

The AIMDx chip excels not only in purification but also in the detection of vital biomarkers. Researchers evaluated its efficacy in isolating and detecting immunoglobulins (IgA, IgG, and IgM) and viral RNA. By integrating acoustic streaming with downstream biosensing chambers, the chip achieves high sensitivity in detecting these markers.

For instance, the device’s ability to detect anti-SARS-CoV-2 S1 receptor-binding domain (RBD) IgA antibodies—linked to COVID-19 severity and vaccine efficacy—was validated. Samples purified using the AIMDx chip showed significantly lower background noise compared to traditional centrifugation methods.

This enhanced detection threshold allowed the identification of rare antibodies at concentrations as low as 15.6 pg/ml, a significant improvement over conventional methods.

The chip’s antibody detection capabilities extend beyond COVID-19. By quantifying IgA, IgG, and IgM levels, it provides a comprehensive profile of a patient’s immune response. This information is critical for diagnosing various infectious diseases and assessing the effectiveness of vaccines. The ability to detect multiple biomarkers simultaneously offers a distinct advantage over single-target diagnostic methods.

A critical component of the AIMDx workflow is its viral lysis module, which rapidly processes samples using acoustic streaming vortices. By mixing purified saliva with a lysis buffer, viral particles are broken down within two minutes, releasing RNA for detection. Transmission electron microscopy (TEM) images confirmed the effectiveness of this approach, showing intact viruses without acoustofluidic lysis and fragmented viral debris after processing.

Subsequent RNA detection leverages reverse transcription loop-mediated isothermal amplification (RT-LAMP) technology, enabling the identification of multiple viral genes. This integrated approach enhances RNA detection sensitivity by 32-fold compared to raw samples, making it a powerful tool for diagnosing infections at early stages. Importantly, this rapid lysis and detection process reduces the time required for diagnostics, enabling quicker medical interventions.

The incorporation of RT-LAMP technology also highlights the versatility of the AIMDx chip. This method is particularly well-suited for point-of-care diagnostics, as it does not require extensive laboratory infrastructure. By combining RT-LAMP with acoustic purification, the chip achieves a level of diagnostic precision previously unattainable in portable devices.

The AIMDx chip’s comprehensive diagnostic capabilities extend beyond purification and lysis. Its antibody detection module provides detailed insights into a patient’s immune response by quantifying IgA, IgG, and IgM levels. By presenting these findings alongside RNA detection results, the chip offers a holistic view of a patient’s health status.

In tests involving saliva samples from COVID-19 patients and healthy controls, the device demonstrated a two- to fivefold increase in antigen detection sensitivity for PCR-positive cases after purification. Healthy control samples showed negligible readouts, confirming the specificity of the AIMDx chip’s detection capabilities. This performance underscores the potential of the chip to deliver reliable results in clinical and field settings.

One of the key advantages of the AIMDx chip is its ability to integrate multiple diagnostic functions onto a single platform. Traditional diagnostic methods often require separate steps for purification, lysis, and detection, each of which demands specialized equipment and expertise. The AIMDx chip streamlines these processes, reducing the time, cost, and labor associated with diagnostic testing.

Traditional diagnostic methods often require extensive laboratory equipment and skilled personnel, limiting their accessibility and scalability. The AIMDx chip addresses these limitations by consolidating multiple diagnostic functions onto a single platform. Its acoustofluidic technology eliminates the need for bulky equipment, making it suitable for point-of-care applications.

Unlike conventional methods, which often rely on centrifugation or filtration for sample preparation, the AIMDx chip offers a compact and automated solution. This innovation reduces labor and costs, paving the way for widespread adoption in healthcare settings. Additionally, its ability to process saliva samples non-invasively makes it an attractive option for patients, particularly those who may be hesitant to undergo blood tests.

The development of the AIMDx chip also highlights the importance of interdisciplinary collaboration in advancing medical technology. By combining principles of physics, engineering, and life sciences, the researchers at Duke University have created a device that addresses multiple diagnostic challenges simultaneously. This holistic approach is essential for tackling complex healthcare problems in an era marked by emerging infectious diseases.

The development of the AIMDx chip comes at a crucial time, as the world continues to face the challenges of emerging infectious diseases. Rapid and accurate diagnostics are essential for implementing timely infection control measures and tailoring medical interventions.

The chip’s ability to provide comprehensive diagnostic data—spanning viral RNA, antigen, and antibody levels—positions it as a valuable tool for pandemic response. By enhancing the detection of viral components and immune markers, it enables healthcare providers to make informed decisions and improve patient outcomes.

The versatility of the AIMDx chip also has implications for broader public health initiatives. Its compact design and portability make it well-suited for deployment in resource-limited settings, where access to traditional laboratory infrastructure may be limited. This capability could significantly enhance global health efforts, particularly in regions disproportionately affected by infectious diseases.

Beyond viral diagnostics, the versatility of the AIMDx chip holds promise for other fields, such as oncology and infectious diseases. Its ability to analyze complex biological samples with high precision could revolutionize diagnostics across a spectrum of medical needs.

For example, the chip could be adapted to detect cancer biomarkers, enabling early diagnosis and improving patient outcomes. Similarly, its application in monitoring chronic diseases could provide valuable insights into disease progression and treatment efficacy. The adaptability of acoustofluidic technology ensures that the AIMDx chip will remain relevant as medical science continues to evolve.

The research team, led by Tony Jun Huang, emphasizes the potential of acoustofluidic technology to drive interdisciplinary innovation. By bridging the fields of physics, engineering, and life sciences, the AIMDx chip exemplifies how scientific advancements can address pressing healthcare challenges. Their work underscores the importance of investing in innovative technologies that have the potential to transform global health.

The AIMDx chip represents a significant leap forward in molecular diagnostics. By integrating purification, lysis, and detection into a single platform, it offers a rapid, non-invasive, and ultrasensitive approach to medical testing. As the global healthcare landscape evolves, innovations like the AIMDx chip will play a pivotal role in enhancing diagnostic accuracy and accessibility, ultimately improving public health outcomes.

The intersection of science and technology has never been more critical. The AIMDx chip demonstrates the power of interdisciplinary research in addressing real-world problems.

As we continue to navigate the challenges of emerging infectious diseases, devices like the AIMDx chip will ensure that healthcare systems are better equipped to respond swiftly and effectively.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

Like these kind of feel good stories? Get The Brighter Side of News' newsletter.