Ultrasensitive detection of bacteria using core-shell nanoparticles and an NMR-filter system.
Ultrasensitive detection of bacteria using core-shell nanoparticles and an NMR-filter system.
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DOI：
10.1002/anie.200901791
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发表时间：
2009
影响因子：
16.6
通讯作者：
Weissleder, Ralph
中科院分区：
文献类型：
--
作者：
Lee, Hakho;Yoon, Tae-Jong;Weissleder, Ralph
病原体的直接检测是对抗人类感染、确定医院来源、调查食物链和生物防御的关键。[1]纳米技术的最新进展使旨在更灵敏和更快地检测病原体的新诊断平台[2]得以开发。[3]许多已报道的技术，尽管优雅，但在常规临床环境中往往失败[4]，因为它们仍然需要广泛的样本纯化，使用复杂的测量设置，或者不容易扩展以满足临床需求。在这里，我们报告了一种新的、简单的、基于纳米颗粒的平台，它可以快速检测本地生物样本中的病原体。在这种方法中，细菌被高度磁性纳米颗粒(MNP)作为靶点，浓缩到微流体室中，并通过核磁共振(NMR)进行检测。我们的诊断平台通过检测结核病(TB)的临床应用进行了评估，结核病是全球主要的疾病和死亡原因。[5]使用卡介苗(BCG)作为结核分枝杆菌的替代品，我们展示了前所未有的检测速度和灵敏度；在30分钟内，仅在痰中检测到20个菌落形成单位(CFU)(1毫升)。新的检测平台具有快速、简单和便携的操作能力，可以成为理想的临床点诊断工具，特别是在资源有限的情况下。诊断始于样本采集和细菌特异性MNP的培养(支持信息图S1)。MNP与细菌壁结合，使细菌具有超顺磁性。在随后的步骤中，用核磁共振测量了整个样品的自旋-自旋弛豫时间(T2)。由于来自MNP的磁场使水质子中核自旋的进动反相[6，7]，每个MNP标记的细菌可以缩短周围数十亿水分子的T2。为了提高检测灵敏度，我们采用了信号放大方案，使其能够在相对较大的样本量中检测到少量细菌。在纳米粒子水平上，通过合成具有高横向弛豫系数(R2)的铁基MnP来增强检测信号。
Direct detection of pathogens is key in combating human infections, in identifying nosocomial sources, in surveying food chains and in biodefense.[1] Recent advances in nanotechnology have enabled the development of new diagnostic platforms [2] aimed at more sensitive and faster pathogen detection.[3] Many of the reported technologies, albeit elegant, often fail in routine clinical settings [4] because they still require extensive specimen purification, use complex measurement setups, or are not easily scalable for clinical demands. Here we report a new, simple, nanoparticle-based platform that can rapidly detect pathogens in native biological samples. In this approach, bacteria are targeted by highly magnetic nanoparticles (MNP), concentrated into a microfluidic chamber, and detected by nuclear magnetic resonance (NMR). The clinical utility of our diagnostic platform was evaluated by detecting tuberculosis (TB), a leading cause of disease and death worldwide.[5] Using the bacillus Calmette-Guérin (BCG) as a surrogate for Mycobacterium tuberculosis, we demonstrate unprecedented detection speed and sensitivity; as few as 20 colony-forming unit (CFU) in sputum (1 mL) were detected in< 30 min. With the capability for fast, simple and portable operation, the new detection platform could be an ideal point-of-care diagnostic tool, especially in resource-limited settings.The diagnosis starts with specimen collection and incubation with bacteria specific MNP (Supporting Information Figure S1). MNP bind to the bacterial wall, rendering the bacteria superparamagnetic. In a subsequent step the spin-spin relaxation time (T2) of the whole sample is measured by NMR. As the magnetic fields from MNP dephase the precession of nuclear spins in water protons [6, 7], each MNP-tagged bacterium can shorten the T2 of billions of surrounding water molecules. To increase detection sensitivity, we have incorporated signal amplification schemes that made it possible to detect small quantities of bacteria in relatively large sample volumes. At the nanoparticle level, the detection signal has been enhanced by synthesizing Fe-based MNP with the high transverse relaxivity (r2).
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作者：
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