Scientists at Nanyang Technological University, Singapore (NTU Singapore), have developed a coin-sized chip that can directly isolate blood plasma from a tube of blood in just 30 minutes, which is more convenient and user-friendly as compared to the current gold standard, multi-step centrifugation process.
Named ExoArc, in just one step, it can achieve high blood plasma purity by removing more than 99.9 per cent of blood cells and platelets precisely and gently. This will greatly speed up clinical analysis of the cell-free DNA and RNA molecules, as well as nanoparticles commonly known as extracellular vesicles. These particles are often used to screen for biomarkers that are tell-tale signs specific to certain cancers and diseases.
Currently, the only way to isolate blood plasma is through using a centrifuge, which spins blood samples at high speeds, separating the blood cells from the plasma. However, even after two rounds of spinning in the centrifuge, there will still be some cells and platelets present in the blood plasma which can break down or degrade, releasing additional bio-content, thus leading to unwanted materials that affect the accuracy of diagnostic tests.
As a proof-of-concept, the team built a portable prototype device (measuring 30cm x 20cm x 30cm) to house the ExoArc chip (3.5cm x 2.5cm x 0.3cm), which has a large touch-screen interface to adjust settings, as well as internal pumps and pipings for the processing of blood samples and collection of the isolated blood plasma.
Together with clinician-scientists from National Cancer Centre Singapore (NCCS), Tan Tock Seng Hospital (TTSH), and the Agency for Science, Technology and Research (A*STAR), the team clinically validated ExoArc by analysing the microRNA profile of blood plasma in healthy people and cancer patients using a biomarker panel and found it was able to diagnose non-small cell lung cancer with a sensitivity of 90%.
As an innovation, ExoArc currently has two patent applications filed through NTUitive, NTU’s innovation and enterprise company and its study findings have been published recently in ACS Nano, a journal under the American Chemical Society.
Pictured above are (left to right) NTU Assoc Prof Hou Han Wei, Research Fellow Dr Leong Sheng Yuan, Research Engineer Ms Lok Wan Wei, and Tan Tock Seng Senior Consultant Assoc Prof Rinkoo Dalan, with the ExoArc prototype system.
Lead scientist of the study, NTU Associate Professor Hou Han Wei, said the team aimed to find a quicker solution that could replace the centrifuge, while still yielding high-quality plasma for disease screening and research.
“It has been nearly 160 years since the invention of the first centrifuge and about 50 years since modern high-speed centrifuges became a standard tool in laboratories for preparing blood samples. Despite these advancements, separating complex liquids like blood, which comprises various cell types and a diverse range of biological materials, remains a challenge,” explained Assoc Prof Hou, a biomedical engineer from the School of Mechanical and Aerospace Engineering and Lee Kong Chian School of Medicine (LKCMedicine).
"By leveraging unique flow phenomenon in tiny channels in a chip that is about the size of a coin, we can now efficiently separate small biological materials based on their size without using any physical membrane or filters. We have transformed this breakthrough technology into a device about size of a small desktop printer, featuring disposable plastic chips to prevent cross-contamination in clinical testing."
In another demonstration of its broad application, the team used ExoArc to study microRNA molecules from blood plasma samples from healthy individuals and those with type 2 diabetes mellitus using quantitative polymerase chain reaction (PCR).
From just one tube of blood, they identified 293 different microRNA molecules. The research team also found that the microRNA profile from plasmas and extracellular vesicles from individuals with type 2 diabetes had a different composition as compared to healthy participants. This suggests the potential of ExoArc in helping to isolate and identify disease-related biomarkers.
- Leong SY, Lok WW, Goh KY, et al. High-Throughput Microfluidic Extraction of Platelet-free Plasma for MicroRNA and Extracellular Vesicle Analysis. ACS Nano. 2024;18(8):6623-6637. doi:10.1021/acsnano.3c12862.
