A coin-sized chip can directly isolate blood plasma from a tube of blood in just 30 minutes, making it quicker than the current multi-step centrifugation process, researchers have reported.
Scientists at Nanyang Technological University, Singapore (NTU Singapore) say their new technology can achieve high blood plasma purity by removing 100% of blood cells and more than 99.9% of platelets precisely and gently in a single step.
Writing in the journal ACS Nano, the team behind the technology say it will speed up clinical analysis of the cell-free DNA and RNA molecules, as well as extracellular vesicles, by removing the need to use a centrifuge.
Even after two rounds of spinning in the centrifuge, some cells and platelets remain present in the blood plasma. These can break down or degrade, releasing cellular debris that affect the accuracy of diagnostic tests, the researchers say.
They built a portable prototype device to house an ExoArc chip, an inertial microfluidic device. With clinician-scientists from National Cancer Centre Singapore (NCCS), Tan Tock Seng Hospital (TTSH), and the Agency for Science, Technology and Research (A*STAR), they undertook clinical validation by analysing the microRNA profile of blood plasma in healthy people and cancer patients using a biomarker panel. They found it was able to diagnose non-small cell lung cancer with a sensitivity of 90%.
Lead study scientist NTU Associate Professor Hou Han Wei, of the School of Mechanical and Aerospace Engineering and Lee Kong Chian School of Medicine (LKCMedicine), said the team aimed to find a fast solution to replacing the centrifuge while 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,” he 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 size of a small desktop printer, featuring disposable plastic chips to prevent cross-contamination in clinical testing."
The team also 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 one tube of blood, they identified 293 different microRNA molecules, finding the microRNA profile from plasmas and extracellular vesicles from individuals with type 2 diabetes had a different composition than that from healthy participants.
Associate Professor Rinkoo Dalan, senior consultant specialising in diabetes and endocrinology at Tan Tock Seng Hospital, said the initial results are promising and show the potential of the new technology 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. 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,” she added.
Source:
Leong SY, Lok WW, Goh KY, Ong HB, Tay HM, Su C, Kong F, Upadya M, Wang W, Radnaa E, Menon R, Dao M, Dalan R, Suresh S, Lim DW, Hou HW. (2024) “High-Throughput Microfluidic Extraction of Platelet-free Plasma for MicroRNA and Extracellular Vesicle Analysis.” ACS Nano, 13 February 2024, doi: 10.1021/acsnano.3c12862.
Link: https://pubs.acs.org/doi/10.1021/acsnano.3c12862
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