Nanobead etectrokinetics: The enabling microfluidic platform for rapid multi-target pathogen detection
Nanobead etectrokinetics: The enabling microfluidic platform for rapid multi-target pathogen detection
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DOI：
10.1002/aic.11286
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发表时间：
2007-10-01
期刊：
影响因子：
3.7
通讯作者：
Chang, Hsueh-Chia
中科院分区：
文献类型：
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作者：
Chang, Hsueh-Chia
Dielectrophoresis （DEP）是一种电动纳米球操作技术，可以为多靶点高通量生物标志物/DNA筛选和微型诊断试剂盒提供强大的连续流微流控平台的最后一部分。这两项技术都有望为化学工程师创造巨大的研究和就业机会。DEP平台具有灵敏度、快速响应（< 10分钟）、现场便携性、可靠性、无与伦比的经济性，并提供了一个可以进行多目标分析的平台。集成的单芯片电动模块，具有嵌入式DEP微电极和其他流量控制组件，特别适用于便携式设备或作为并行网络中的单元。本文回顾了电动平台的优点，特别是DEP组件，以及实现这种平台所面临的剩余技术和科学挑战。诊断分析是用于检测和鉴定病原体（有害细菌、病毒、生物体等）和病变细胞或它们释放的分子生物标志物的生化技术。在过去的二十年里，诊断分析科学的研究取得了爆炸式的突破。由于这些进展，病原体诊断已大大提高了速度、特异性、敏感性和现场适用性。可以说，与该领域相关的圣杯是它提供早期和快速癌症检测的能力。尽管几十年来癌症药物的发展，大多数癌症患者的死亡率仍然高得令人无法接受，如果诊断是在疾病进展的后期。相比之下，癌症的早期和特定类型的诊断将立即显著降低这一不可接受的死亡率。同样，对脓毒症等急性感染的快速和病原体特异性诊断也会显著提高患者的存活率。脓毒症是一种致命的、快速的血液细菌感染，通常在几天内就会致命。除了速度和特异性外，允许现场使用的设备便携性也是非常可取的。便携性对于现场应用将特别有用，例如流行病控制（例如在机场识别严重急性呼吸系统综合症（SARS）或禽流感病毒），检测食品和水源中的大肠杆菌，以及在第三世界国家识别抗抗体结核病（TB）或疟疾细菌。对于面向消费者的诊断试剂盒，便携式试剂盒的样品接触组件必须是一次性的，因此，制造一次性的经济是重要的。与癌症生物标志物不同，医学病原体通常以相对较大的浓度出现。相比之下，生物恐怖主义和环境应用通常涉及的目标数量较少，敏感性是一个主要问题。简而言之，特异性、速度和灵敏度是诊断分析的关键性能指标，便携性和经济性对现场使用的试剂盒也很重要。根据这些衡量标准，最近诊断科学的科学突破具有变革性，并对医疗保健、环境监测和生物技术产业产生了巨大影响。例如，用抗生素筛选检测细菌的百年培养技术需要几天的时间，而在过去十年中开发的用于同样任务的现代免疫测定法通常只需要几个小时。这种戏剧性的进步和疯狂的研究活动是由聚合酶链反应（PCR）的发明和随后的发展催化的，它不仅通过允许快速DNA克隆而彻底改变了分子遗传学，而且还…
Dielectrophoresis (DEP) is an electrokinetic nanobead-manipulation technique that can provide the final piece of a robust continuous-flow microfluidic platform for multitarget high-throughput biomarker/DNA screening and miniature diagnostic kits. Both technologies promise to create enormous research and employment opportunities for Chemical Engineers. The DEP platform offers sensitivity, rapid response (< 10 min), field portability, reliability, unmatched economy, and provides a platform from which multitarget analysis can be performed. An integrated single-chip electrokinetic module, with embedded DEP microelectrodes and other flow-control components, is especially suitable for a portable device or as a unit in a parallelized network. This article reviews the advantages of an electrokinetic platform, particularly the DEP components, and the remaining technical and scientific challenges facing the realization of such a platform. Diagnostic assays are biochemical techniques for detecting and identifying pathogens (harmful bacteria, viruses, organisms, etc.,) and diseased cells, or the molecular biomarkers they release. In the last two decades, there has been an explosion of research breakthroughs in diagnostic assay science. As a result of these advances, pathogen diagnostics has become dramatically more rapid, specific, sensitive and field-applicable. Arguably, the holy grail associated with this field is its capacity to provide for early and rapid cancer detection. Despite decades of cancer drug development, the mortality rate for most cancer patients remains unacceptably high if the diagnosis is made late in the disease progression. In contrast, early and type-specific diagnosis of cancer would immediately and dramatically lower this unacceptable mortality rate. Similarly, swift and pathogen-specific diagnosis of acute infections like sepsis, a deadly and rapid bacteria infection of the blood that is often lethal in a matter of days, would also significantly increase the patient survival rate. In addition to speed and specificity, device portability allowing for field use is also highly desirable. Portability would be particularly useful for field applications, such as epidemic control (identifying severe acute respiratory syndrome (SARS), or avian-flu viruses at airports, for example), detecting E. Coli in food products and water sources, and identifying antibody-resistant tuberculosis (TB), or malaria bacteria in third-world countries. For consumer oriented diagnostic kits, the sample-contacting components of the portable kit must be disposable, and, hence, the economy of fabricating the disposables is important. Unlike cancer biomarkers, medical pathogens typically appear in relatively large concentrations. In contrast, bioterrorism and environmental applications often involve smaller number of targets, and sensitivity is a main issue. In short, specificity, speed and sensitivity are the key performance measures for diagnostic assays, with portability and economy also important for field-intended kits. As gauged by these measures, recent scientific breakthroughs in diagnostic science have been transformative, and have had enormous implications on health care, environmental monitoring, and the biotechnology industry. For example, the century-old culturing technique of detecting bacteria with antibiotic screening requires days, whereas modern immunoassays for the same task, developed in the last decade, often take only hours.Such dramatic advances and frenzied research activity has been catalyzed by the invention and subsequent development of the polymerase chain reaction (PCR), which not only revolutionized molecular genetics by allowing rapid DNA cloning, but also …