NEW YORK – A new low-cost tuberculosis (TB) test that requires no lab facilities and little specialist training might be able to help fill healthcare gaps in remote and low-resource settings.

纽约——一种新的低成本结核病（TB）检测方法，不需要实验室设备，也不需要太多专业培训，或许可以帮助填补偏远和资源匮乏地区的医疗保健缺口。

The Lab-in-a-Tube TB (LIT-TB) test is being developed by scientists at Tulane University, who published the results of a pilot study of the device Wednesday in

杜兰大学的科学家们正在开发这种“试管实验室”TB（LIT-TB）测试，他们于周三发表了该设备的一项初步研究结果。

Science Translational Medicine

科学转化医学

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To run the LIT-TB test, blood, saliva, or sputum is collected in an assay tube, which is then transferred to the incubator port of a portable device for solubilization and inactivation. A plunger loads the lysate onto a DNA capture membrane and initiates a recombinase polymerase amplification (RPA) reaction involving a CRISPR-Cas12a system.

进行LIT-TB测试时，将血液、唾液或痰液收集在检测管中，然后转移到便携式设备的孵育端口进行溶解和灭活。柱塞将裂解物加载到DNA捕获膜上，并启动涉及CRISPR-Cas12a系统的重组酶聚合酶扩增（RPA）反应。

Once this reaction is complete, the tube is transferred to a readout port where a fluorescent signal indicating the presence of the TB bacterium is detected and analyzed..

一旦该反应完成，试管被转移到一个读取端口，在那里检测并分析表示存在结核杆菌的荧光信号。

The assay was tested in serum samples from a cohort of 27 children from the Dominican Republic, diagnosed with either pulmonary or extrapulmonary TB (PTB and EPTB, respectively), and 35 children who were close contacts of the others but had no evidence of infection.

该检测方法在来自多米尼加共和国的 27 名儿童的血清样本中进行了测试，这些儿童被诊断为患有肺结核或肺外结核（分别为 PTB 和 EPTB），同时测试的还有 35 名与前者密切接触但没有感染证据的儿童。

The investigators compared LIT-TB's performance to traditional lab culture and to Cepheid's GeneXpert MTB/RIF assay. Although specimen culture is often considered the gold standard for diagnosing TB, GeneXpert is more sensitive and faster than culture and is recognized as a valid TB diagnostic platform by both the World Health Organization and the US Food and Drug Administration, said Tony Hu, a molecular biologist at Tulane University and the senior author of the study..

研究人员将LIT-TB的性能与传统的实验室培养和Cepheid公司的GeneXpert MTB/RIF检测进行了比较。杜兰大学的分子生物学家、该研究的资深作者胡东尼表示，虽然标本培养常被认为是诊断结核病的黄金标准，但GeneXpert比培养更敏感且速度更快，并且被世界卫生组织和美国食品药品监督管理局认可为有效的结核病诊断平台。

In Hu's study, LIT-TB demonstrated an overall better sensitivity than the comparators in this cohort: 81 percent for LIT-TB, 55 percent for lab culture, and 68 percent for the GeneXpert MTB/RIF.

在胡的研究中，LIT-TB 在该队列中表现出比其他检测方法更高的整体敏感性：LIT-TB 为 81%，实验室培养为 55%，GeneXpert MTB/RIF 为 68%。

The researchers tested the children over the course of their treatments and observed the LIT-TB signal decrease in both types of TB as the children's health improved, suggesting that the test can also be used to monitor treatment.

研究人员在治疗过程中对儿童进行了测试，观察到随着儿童健康状况的改善，两种肺结核患者的LIT-TB信号均有所下降，这表明该测试还可用于监测治疗效果。

Hu added that another key finding in this cohort was that LIT-TB successfully identified six of the eight children with EPTB.

胡补充说，该队列的另一个关键发现是，LIT-TB成功识别了8名患有EPTB的儿童中的6名。

'This is quite important for pediatric TB management,' he said, as EPTB is generally harder to diagnose than PTB, owing to its more diverse clinical presentations and greater difficulty in obtaining samples.

“这对于儿童结核病的管理来说非常重要，”他说，由于其临床表现更多样化且更难获取样本，EPTB通常比PTB更难诊断。

As an added measure, Hu and his colleagues also tested saliva samples from a case-control cohort of 15 adults diagnosed with TB and 15 healthy controls. The LIT-TB assay identified 11 true positives and no false positives among this group.

作为一项额外的措施，胡和他的同事还测试了一个由15名被诊断为结核病的成人和15名健康对照者组成的病例对照队列的唾液样本。LIT-TB检测在这组中识别出11例真阳性，且没有假阳性。

Similar results also came from an analysis of 71 sputum samples obtained from 36 adults with suspected TB. Here, LIT-TB demonstrated 100 percent sensitivity across the board, with specificities between approximately 87 and 91 percent for individuals with TB, nontuberculous mycobacteria infections, and no evidence of TB infection.

对从36名疑似结核病成人获取的71份痰液样本的分析也得出了类似结果。在此，LIT-TB总体显示出100%的敏感性，对结核病患者、非结核分枝杆菌感染者以及无结核感染证据者的特异性介于约87%至91%之间。

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Mikashmi Kohli, senior scientist for evidence and policy at global nonprofit research organization FIND, whose research has focused on TB diagnostics, called the LIT-TB findings 'very interesting' with respect to both diagnostic performance and treatment response monitoring, while also drawing attention to the study's small size and single geographical site.

全球非营利研究机构FIND的证据与政策高级科学家米卡什米·科利（Mikashmi Kohli）专注于结核病诊断研究，她称LIT-TB的研究结果在诊断性能和治疗反应监测方面“非常有趣”，同时也指出了该研究规模较小且仅在一个地理地点进行。

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'I think this is a great start for something very innovative, and I am happy to see the design and use cases of this test,' Kohli said via email. She cautioned, however, that the LIT-TB technology should be evaluated in more presumptive cases of PTB and EPTB, both for diagnostic performance and for monitoring treatment response, and the evidence should come from larger and more diverse cohorts from different regions..

“我认为这是一个非常创新的事物的良好开端，我很高兴看到这项测试的设计和用例，”科利通过电子邮件表示。然而，她警告说，LIT-TB 技术应该在更多疑似 PTB 和 EPTB 病例中进行评估，既包括诊断性能，也包括监测治疗反应，且证据应来自更大、更多样化、来自不同地区的人群。

Hu acknowledged the study's small size and homogeneous cohort, saying that larger and more diverse studies are currently being planned. 'Ultimately we need a better cohort to validate,' he said.

胡承认这项研究规模较小，且队列同质性较高，并表示目前正计划进行更大规模、更多样化的研究。他说：“最终我们需要一个更好的队列来进行验证。”

The LIT-TB assay is designed to be simple, stable to a broad range of temperature changes, and cheap. Hu said that the entire process from sample to result takes approximately 45 minutes to run. The reader costs roughly between $700 and $800 in components, all of which can be ordered via Amazon, and it costs approximately $2.70 to run each sample.

LIT-TB检测方法设计简单，对大范围的温度变化稳定且成本低。胡说，从样本到结果的整个过程大约需要45分钟。该读取设备的组件成本大约在700至800美元之间，所有组件均可通过亚马逊订购，每个样本的运行成本约为2.70美元。

Hu estimates that this price will drop further when the test can be made at scale. .

胡估计，当测试可以大规模进行时，这个价格会进一步下降。

By comparison, prices for the GeneXpert MTB/RIF benchtop device range from

相比之下，GeneXpert MTB/RIF台式设备的价格范围从

approximately $9,000 to $72,000

大约 9,000 至 72,000 美元

, with costs per cartridge ranging between roughly $10 to $25, although reduced pricing options are available for low-income regions through the

，每盒费用大约在10到25美元之间，不过通过该机构，低收入地区可以享受降价选项。

Global Fund

全球基金

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Tulane University holds the LIT-TB patent and IntelliGenome, a diagnostics company cofounded by Hu, is currently negotiating with the university for the right to license it.

杜兰大学持有LIT-TB专利，而由胡共同创立的诊断公司IntelliGenome目前正在与该校谈判以获取该专利的许可权。

Hu said that the goal is to acquire a nonexclusive license, since the LIT-TB technology is essentially a platform technology with a wide range of potential applications and should be made available to all who can use it.

胡说，目标是获得非独家许可，因为LIT-TB技术本质上是一种平台技术，具有广泛的潜在应用，应该提供给所有能使用它的人。

'You can really [apply] this to many tests,' he said, adding that his own lab at Tulane is currently exploring its uses in syphilis and pneumonia.

“你真的可以[应用]这个到很多测试中，”他说道，并补充说他在杜兰大学的实验室目前正在探索其在梅毒和肺炎中的用途。

Although the licensing negotiations have not yet finished, Hu said that IntelliGenome has been making plans for the clinical trials that would be needed for regulatory submission.

虽然许可谈判尚未结束，但胡表示 IntelliGenome 一直在为监管提交所需的临床试验制定计划。

'[IntelliGenome] is having a very active conversation with the FDA, and it will start a clinical trial very soon,' Hu said, noting that the company has identified three trial sites in Germany, Mexico, and the US.

“[IntelliGenome]正与FDA进行非常积极的对话，并将很快开始临床试验，”胡说，他指出公司已经确定了在德国、墨西哥和美国的三个试验地点。

In addition to TB testing, IntelliGenome is also developing RPA-CRISPR-based diagnostic assays for nontuberculous mycobacteria infection and mycobacterium avium complex and is exploring possibilities in the oncology space. The company currently markets a benchtop version of the LIT-TB test that Hu

除了结核病检测，IntelliGenome 还在开发基于RPA-CRISPR的非结核分枝杆菌感染和鸟分枝杆菌复合体的诊断分析方法，并正在探索肿瘤学领域的可能性。该公司目前在市场上推出了一款LIT-TB测试的台式版本，胡先生表示。

developed previously

之前开发的

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Hu said that such low-cost and simple-to-use tests are crucial for TB testing in remote areas and those with limited infrastructure and resources.

胡说，这种低成本且易于使用的测试对于在偏远地区以及基础设施和资源有限的地方进行结核病检测至关重要。

Most current technology on the market, Hu said, relies on benchtop handling and in many low- to middle-income countries (LMICs), these are often placed in central lab facilities in urban areas, making it more expensive and logistically complicated to gather and analyze samples.

胡说，目前市场上的大多数技术都依赖于台式操作，并且在许多低收入和中等收入国家（LMICs），这些设备通常被放置在城市地区的中心实验室，使得收集和分析样本更加昂贵且物流复杂。

The World Health Organization estimates that globally, TB is the leading cause of death from a single infectious disease. It also estimates that the vast majority of cases occur in LMICs, with some two-thirds of global cases coming from just eight countries: India, Indonesia, China, the Philippines, Pakistan, Nigeria, Bangladesh, and the Democratic Republic of Congo..

世界卫生组织估计，全球范围内，结核病是单一传染病的首要致死原因。它还估计绝大多数病例发生在中低收入国家，其中约三分之二的全球病例来自八个国 家：印度、印度尼西亚、中国、菲律宾、巴基斯坦、尼日利亚、孟加拉国和刚果民主共和国。

Even higher-income countries stand to benefit from the availability of a rapid and low-cost TB test. The US, for instance,

即使是较高收入的国家，也能从快速且低成本的结核病检测方法的可用性中受益。例如，美国，

recently cut funding

最近削减了资金支援

to several programs that supported TB testing. The WHO has previously said that the US has funded nearly a quarter of global TB testing and treatment programs over the past 20 years.

对几个支持结核病检测的项目而言。世卫组织此前曾表示，在过去二十年中，美国资助了全球近四分之一的结核病检测和治疗项目。

In addition to advancing the development of LIT-TB, Hu has been designing a self-powered microfluidic chip for detecting TB infection. A paper detailing that device, Hu said, was just accepted to

除了推进LIT-TB的开发，胡还在设计一种用于检测结核感染的自供电微流控芯片。胡表示，详细介绍该设备的论文刚刚被接受。

Nature Biomedical Engineering

《自然-生物医学工程》

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'This test is going to make TB testing more convenient,' Hu said, 'especially for people living in resource-limited areas where a central lab is not available to them. I think that's going to hopefully change the landscape.'

“这项测试将使结核病检测更加便捷，”胡说，“尤其是对于那些生活在资源有限地区、无法使用中心实验室的人们。我希望这能带来改变。”