Coin-sized device can isolate plasma, replacing centrifuges

Scientists at Nanyang Technological University, Singapore (NTU Singapore) have developed a coin-sized chip that can directly isolate plasma from a tube of blood in just 30 min, which is more convenient and user-friendly than the current gold-standard, multi-step centrifugation process.

Named ExoArc and described in the journal ACS Nano, the chip can achieve high blood plasma purity by removing more than 99.9% of blood cells and platelets precisely and gently in just one step. This should greatly speed up clinical analysis of the cell-free DNA and RNA molecules as well as extracellular vesicles, which are often used to screen for biomarkers that are telltale signs specific to certain cancers and diseases.

The current gold-standard method of isolating blood plasma relies on a centrifuge, which spins blood samples at high speeds, separating the blood cells from the plasma. But even after two rounds of spinning in the centrifuge, which can take up to an hour, there will still be some cells and platelets present in the blood plasma which can break down or degrade, leading to unwanted materials that affect the accuracy of diagnostic tests. This is one of the reasons that blood tests are time-sensitive, requiring processing within a day or even a few hours to prevent this rapid degradation of biological material.

Laboratories typically wait to accumulate multiple blood samples before using the centrifuge, extending the isolation process by several hours. This delay, combined with the extended duration of centrifugation and operator variability, sometimes makes it challenging to compare scientific findings between different research labs. Associate Professor Hou Han Wei, lead scientist on the new study, said the NTU 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,” Hou said. “Despite these advancements, separating complex liquids like blood, which comprises various cell types and a diverse range of biological materials, remains a challenge.

“By leveraging unique flow phenomenon in tiny channels in a chip that is about the size of a dollar 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 the size of a small desktop printer, featuring disposable plastic chips to prevent cross-contamination in clinical testing.”

Assoc Prof Hou Han Wei holding the patent-pending ExoArc chip. Image credit: NTU Singapore.

As a proof of concept, the NTU team built a portable prototype device (measuring 30 x 20 x 30 cm) to house the ExoArc chip (3.5 x 2.5 x 0.3 cm), 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. Unlike a centrifuge, which usually processes multiple tubes of blood samples, ExoArc technology can be scaled up by designing multiple channels to simultaneously isolate blood plasma as and when blood samples are received in clinics or hospitals in a faster and more consistent manner.

Together with clinician-scientists from the 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%. Co-author Professor Darren Lim, Senior Consultant in the Division of Medical Oncology at NCCS, said reducing contamination from degraded blood cells is crucial for the accuracy of diagnostic tests.

“Our study shows that this device allows quicker and more precise clinical diagnoses, significantly decreasing the waiting time for test results, reducing patients’ anxiety and ultimately improving their overall care,” Lim said. “This is particularly significant for cancer treatment.”

Prototype of the ExoArc system. Image credit: NTU Singapore.

In another demonstration of its 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.

Associate Professor Rinkoo Dalan, Senior Consultant specialising in diabetes and endocrinology at TTSH, said the initial results are promising and show the potential of ExoArc being able to help drive precision medicine.

“This technology can help clinicians better predict and manage complications of chronic metabolic conditions like diabetes, by providing more accurate, timely and individualised information,” Dalan said. “By detecting specific biomarkers accurately, we can tailor treatments to the unique needs of each patient, potentially improving outcomes and enhancing the quality of care.”

With two patent applications now filed for the ExoArc innovation through NTUitive, NTU’s innovation and enterprise company, it is believed that the method has the potential to significantly reduce the time needed to prepare samples for testing and streamline diagnostics, potentially helping to reduce overall cost. By adjusting the size cut-off, the platform can also be used to isolate bacteria or viruses from blood or other biofluids.

Top image caption: The research team with the ExoArc prototype system. Image credit: NTU Singapore.