新加坡南洋理工大學的科學家發明了一種硬幣大小的

新加坡南洋理工大學的科學家開發了一種名為ExoArc的硬幣大小的晶片，只需30分鐘即可分離血漿，比目前的多步驟離心過程更方便和人性化。 ExoArc 通過去除超過 99.9% 的血球和血小板來實現高血漿純度，從而能夠對遊離 DNA、RNA 和細胞外囊泡進行快速臨床分析以進行生物標記篩選。經過臨床驗證，ExoArc 能夠準確診斷非小細胞肺癌，靈敏度高達 90%，在糖尿病等慢性代謝性疾病的精準醫療中具有潛在應用。

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.

新加坡南洋理工大學（NTU Singapore）的科學家開發出一種硬幣大小的晶片，只需30分鐘即可直接從試管中分離出血漿，與目前的黃金標準相比，更加方便和人性化，多步離心過程。

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.

它被命名為ExoArc，只需一步，即可精確、溫和地去除99.9%以上的血球和血小板，從而達到高血漿純度。

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.

這將大大加快無細胞 DNA 和 RNA 分子以及通常稱為細胞外囊泡的奈米顆粒的臨床分析。這些顆粒通常用於篩選生物標記物，這些生物標記是某些癌症和疾病特有的跡象。

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.

目前，分離血漿的唯一方法是使用離心機，它高速旋轉血液樣本，將血球與血漿分離。

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.

然而，即使在離心機中旋轉兩輪後，血漿中仍會存在一些細胞和血小板，它們會分解或降解，釋放出額外的生物成分，從而產生影響診斷測試準確性的不需要的物質。

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.

作為概念驗證，該團隊構建了一個便攜式原型設備（尺寸為 30 厘米 x 20 厘米 x 30 厘米）來容納 ExoArc 芯片（3.5 厘米 x 2.5 厘米 x 0.3 厘米），該設備具有用於調整設置的大型觸控螢幕介面以及用於處理血液樣本和收集分離血漿的內部幫浦和管道。

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 per cent.

該團隊與新加坡國家癌症中心 (NCCS)、陳篤生醫院 (TTSH) 和新加坡科學技術研究局 (A*STAR) 的臨床醫生科學家一起，透過分析血漿的 microRNA 圖譜對 ExoArc 在健康人和癌症患者中使用生物標記組進行研究，發現它能夠以90% 的靈敏度診斷非小細胞肺癌。

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[1], a journal under the American Chemical Society.

作為一項創新，ExoArc 目前已透過南洋理工大學創新與企業公司 NTUitive 提交了兩項專利申請，其研究成果最近發表在美國化學會旗下期刊 ACS Nano[1] 上。

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.

該研究的首席科學家、南洋理工大學副教授侯漢偉表示，該團隊的目標是找到更快的解決方案來取代離心機，同時仍能產生用於疾病篩檢和研究的高品質血漿。

“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 [2]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).

「距離第一台離心機發明已有近 160 年，現代高速離心機成為實驗室 [2] 製備血液樣本的標準工具已有約 50 年。儘管取得了這些進步，分離像血液這樣包含各種細胞類型和各種生物材料的複雜液體仍然是一個挑戰，」機械與航空航天工程學院和李光前學院的生物醫學工程師侯副教授解釋道。醫學（LKCMedicine ）。

"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."

「透過利用一美元硬幣大小的晶片中微小通道中的獨特流動現象，我們現在可以根據尺寸有效分離小型生物材料，而無需使用任何物理薄膜或過濾器。我們已將這項突破性技術轉化為設備大小與小型桌面印表機相當，具有一次性塑膠晶片，可防止臨床測試中的交叉污染。”

Co-author of the paper, Professor Darren Lim, Senior Consultant in the Division of Medical Oncology at NCCS and Director of Research at the SingHealth Duke-NUS Lung Centre, explained the importance of high-quality blood plasma.

該論文的合著者、NCCS 腫瘤內科高級顧問兼新加坡保健集團杜克-新加坡國立大學肺科中心研究總監 Darren Lim 教授解釋了高品質血漿的重要性。

"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. This is particularly significant for cancer treatment," said Prof Lim.

「減少降解血球的污染對於診斷測試的準確性至關重要。我們的研究表明，該設備可以實現更快、更精確的臨床診斷，顯著減少測試結果的等待時間，減少患者的焦慮並最終改善他們的整體護理。這對於癌症治療尤其重要，」林教授說。

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).            

在其廣泛應用的另一個演示中，該團隊使用 ExoArc 透過定量聚合酶鏈反應 (PCR) 研究健康個體和 2 型糖尿病患者血漿樣本中的 microRNA 分子。

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.

光是從一管血液中，他們就鑑定出了 293 種不同的 microRNA 分子。研究團隊還發現，與健康參與者相比，2 型糖尿病患者血漿和細胞外囊泡的 microRNA 光譜具有不同的組成。這表明 ExoArc 在幫助分離和識別疾病相關生物標記方面具有潛力。

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 ExoArc being able to help drive precision medicine.

陳篤生醫院糖尿病和內分泌學高級顧問 Rinkoo Dalan 副教授表示，初步結果令人鼓舞，並顯示了 ExoArc 能夠幫助推動精準醫療的潛力。

“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,” said Assoc Prof Dalan, who is also a teaching faculty at LKCmedicine.

「這項技術可以透過提供更準確、及時和個人化的信息，幫助臨床醫生更好地預測和管理糖尿病等慢性代謝疾病的併發症。透過準確檢測特定的生物標記物，我們可以根據每位患者的獨特需求量身定制治療方案，從而有可能改善治療效果並提高護理品質。」兼任 LKCmedicine 教學人員的 Dalan 副教授說。

ExoArc vs conventional centrifuge

ExoArc 與傳統離心機對比

The current gold-standard method of isolating blood plasma relies on centrifuges, which is not foolproof and is highly dependent on the skill of the technicians who manually extract the plasma after each spin.

目前分離血漿的黃金標準方法依賴離心機，這並非萬無一失，並且高度依賴每次旋轉後手動提取血漿的技術人員的技能。

Even after two centrifugation rounds, which can take up to an hour, residual biological cells can remain in the plasma, potentially contaminating RNA tests and leading to inaccurate results.

即使經過兩輪離心（可能需要長達一小時），殘留的生物細胞仍可能保留在血漿中，可能污染 RNA 測試並導致結果不準確。

One of the key reasons is that blood tests are time-sensitive, requiring processing within a day or even a few hours to prevent the rapid degradation of biological material from cells. This breakdown introduces additional DNA, RNA or vesicles into the plasma, which can distort test outcomes.

關鍵原因之一是血液檢測對時間敏感，需要在一天甚至幾個小時內處理，以防止細胞中生物材料的快速降解。這種分解會將額外的 DNA、RNA 或囊泡引入血漿，這可能會扭曲測試結果。

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.

實驗室通常會在使用離心機之前等待累積多個血液樣本，從而將分離過程延長了幾個小時。這種延遲加上離心持續時間的延長和操作員的可變性，有時使得比較不同研究實驗室之間的科學發現變得困難。

Unlike the centrifuge machine which usually process 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.

與通常處理多管血液樣本的離心機不同，ExoArc 技術可以透過設計多個通道來擴大規模，以便在診所或醫院以更快、更一致的方式接收血液樣本時同時分離血漿。

In future, this process could be automated into a one-step process, which would significantly reduce the time needed to prepare samples for testing and will streamline the diagnostic process, potentially helping to reduce overall cost. By adjusting the size-cutoff, this platform technology can also be used to isolate bacteria or viruses from blood or other biofluids.

將來，此過程可以自動化為一步式流程，這將顯著減少準備測試樣本所需的時間，並簡化診斷過程，可能有助於降低整體成本。透過調整尺寸截止值，此平台技術還可用於從血液或其他生物流體中分離細菌或病毒。

The development of ExoArc is backed by a Proof-of-Concept and Proof-of-Value grant from the NTUitive Gap Fund, under the NTU Innovation and Entrepreneurship initiative. This initiative seeks to turn research into practical innovations that address societal challenges, like an ageing population, and generate significant economic benefits for Singapore.

ExoArc 的開發得到了南洋理工大學創新與創業計劃下的 NTUitive Gap 基金的概念驗證和價值證明贈款的支持。該倡議旨在將研究轉化為實際創新，解決人口老化等社會挑戰，並為新加坡帶來顯著的經濟效益。

The study also included contributions from scientists at the Massachusetts Institute of Technology and the University of Texas Medical Branch (Galveston).

該研究還包括麻省理工學院和德克薩斯大學醫學分校（加爾維斯頓）科學家的貢獻。

[1] ACS Nano 2024, 18, 8, 6623–6637, Publication Date: February 13, 2024,

[1] ACS Nano 2024, 18, 8, 6623–6637，出版日期：2024 年 2 月 13 日，

https://doi.org/10.1021/acsnano.3c12862

https://doi.org/10.1021/acsnano.3c12862

[2] Marshall Scientific. (n.d.). The history of the centrifuge. Retrieved from https://www.marshallscientific.com/the_history_of_the_centrifuge_a/349.htm

[2] 馬歇爾科學。 （日期不詳）。離心機的歷史。取自 https://www.marshallscientific.com/the_history_of_the_centrifuge_a/349.htm