新加坡南洋理工大学的科学家发明了一种硬币大小的

新加坡南洋理工大学的科学家开发了一种名为ExoArc的硬币大小的芯片，只需30分钟即可分离血浆，比目前的多步离心过程更加方便和人性化。 ExoArc 通过去除超过 99.9% 的血细胞和血小板来实现高血浆纯度，从而能够对游离 DNA、RNA 和细胞外囊泡进行快速临床分析以进行生物标志物筛选。经过临床验证，ExoArc 能够准确诊断非小细胞肺癌，灵敏度高达 90%，在糖尿病等慢性代谢性疾病的精准医疗中具有潜在应用。

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.

新加坡南洋理工大学（NTU Singapore）的科学家开发出一种硬币大小的芯片，只需30分钟即可直接从试管中分离出血浆，与目前的金标准相比，更加方便和人性化，多步离心过程。

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.

它被命名为ExoArc，只需一步，即可精确、温和地去除99.9%以上的血细胞和血小板，从而达到高血浆纯度。

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.

这将大大加快无细胞 DNA 和 RNA 分子以及通常称为细胞外囊泡的纳米颗粒的临床分析。这些颗粒通常用于筛选生物标志物，这些生物标志物是某些癌症和疾病特有的迹象。

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，分离血浆的唯一方法是使用离心机，它高速旋转血液样本，将血细胞与血浆分离。

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，即使在离心机中旋转两轮后，血浆中仍会存在一些细胞和血小板，它们会分解或降解，释放出额外的生物成分，从而产生影响诊断测试准确性的不需要的物质。

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.

作为概念验证，该团队构建了一个便携式原型设备（尺寸为 30 厘米 x 20 厘米 x 30 厘米）来容纳 ExoArc 芯片（3.5 厘米 x 2.5 厘米 x 0.3 厘米），该设备具有用于调整设置的大型触摸屏界面以及用于处理血样和收集分离血浆的内部泵和管道。

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.

该团队与新加坡国家癌症中心 (NCCS)、陈笃生医院 (TTSH) 和新加坡科学技术研究局 (A*STAR) 的临床医生科学家一起，通过分析血浆的 microRNA 图谱对 ExoArc 进行了临床验证在健康人和癌症患者中使用生物标记物组进行研究，发现它能够以 90% 的灵敏度诊断非小细胞肺癌。

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.

作为一项创新，ExoArc 目前已通过南洋理工大学创新与企业公司 NTUitive 提交了两项专利申请，其研究成果最近发表在美国化学会旗下期刊 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.

该研究的首席科学家、南洋理工大学副教授侯汉伟表示，该团队的目标是找到一种更快的解决方案来取代离心机，同时仍能产生用于疾病筛查和研究的高质量血浆。

“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).

“距离第一台离心机发明已有近 160 年，现代高速离心机成为实验室 [2] 制备血液样本的标准工具已有约 50 年。尽管取得了这些进步，分离像血液这样包含各种细胞类型和各种生物材料的复杂液体仍然是一个挑战，”机械与航空航天工程学院和李光前学院的生物医学工程师侯副教授解释道。医学（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."

“通过利用一美元硬币大小的芯片中微小通道中的独特流动现象，我们现在可以根据尺寸有效分离小型生物材料，而无需使用任何物理膜或过滤器。我们已将这项突破性技术转化为设备大小与小型桌面打印机相当，具有一次性塑料芯片，可防止临床测试中的交叉污染。”

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.

该论文的合著者、NCCS 肿瘤内科高级顾问兼新加坡保健集团杜克-新加坡国立大学肺科中心研究总监 Darren Lim 教授解释了高质量血浆的重要性。

"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.

“减少降解血细胞的污染对于诊断测试的准确性至关重要。我们的研究表明，该设备可以实现更快、更精确的临床诊断，显着减少测试结果的等待时间，减少患者的焦虑并最终改善他们的整体护理。这对于癌症治疗尤其重要，”林教授说。

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).            

在其广泛应用的另一个演示中，该团队使用 ExoArc 通过定量聚合酶链反应 (PCR) 研究健康个体和 2 型糖尿病患者血浆样本中的 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.

仅从一管血液中，他们就鉴定出了 293 种不同的 microRNA 分子。研究小组还发现，与健康参与者相比，2 型糖尿病患者血浆和细胞外囊泡的 microRNA 谱具有不同的组成。这表明 ExoArc 在帮助分离和识别疾病相关生物标志物方面具有潜力。

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.

陈笃生医院糖尿病和内分泌学高级顾问 Rinkoo Dalan 副教授表示，初步结果令人鼓舞，并显示了 ExoArc 能够帮助推动精准医疗的潜力。

“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.

“这项技术可以通过提供更准确、及时和个性化的信息，帮助临床医生更好地预测和管理糖尿病等慢性代谢疾病的并发症。通过准确检测特定的生物标志物，我们可以根据每位患者的独特需求定制治疗方案，从而有可能改善治疗效果并提高护理质量。”兼任 LKCmedicine 教学人员的 Dalan 副教授说道。

ExoArc vs conventional centrifuge

ExoArc 与传统离心机对比

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.

目前分离血浆的黄金标准方法依赖于离心机，这并非万无一失，并且高度依赖于每次旋转后手动提取血浆的技术人员的技能。

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.

即使经过两轮离心（可能需要长达一个小时），残留的生物细胞仍可能保留在血浆中，可能污染 RNA 测试并导致结果不准确。

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.

关键原因之一是血液检测对时间敏感，需要在一天甚至几个小时内进行处理，以防止细胞中生物材料的快速降解。这种分解会将额外的 DNA、RNA 或囊泡引入血浆，这可能会扭曲测试结果。

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.

实验室通常会在使用离心机之前等待积累多个血液样本，从而将分离过程延长了几个小时。这种延迟加上离心持续时间的延长和操作员的可变性，有时使得比较不同研究实验室之间的科学发现变得困难。

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.

与通常处理多管血液样本的离心机不同，ExoArc 技术可以通过设计多个通道来扩大规模，以便在诊所或医院以更快、更一致的方式接收血液样本时同时分离血浆。

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.

将来，这一过程可以自动化为一步式过程，这将显着减少准备测试样品所需的时间，并简化诊断过程，可能有助于降低总体成本。通过调整尺寸截止值，该平台技术还可用于从血液或其他生物流体中分离细菌或病毒。

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 的开发得到了南洋理工大学创新与创业计划下的 NTUitive Gap 基金的概念验证和价值证明赠款的支持。该倡议旨在将研究转化为实际创新，解决人口老龄化等社会挑战，并为新加坡带来显着的经济效益。

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

该研究还包括麻省理工学院和德克萨斯大学医学分校（加尔维斯顿）科学家的贡献。

[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] 马歇尔科学。 （日期不详）。离心机的历史。检索自 https://www.marshallscientific.com/the_history_of_the_centrifuge_a/349.htm