An Integrated Lab-on-a-Transistor for Biological Detection

发达世界和发展中世界（全球卫生领域）在传染病管理方面的危机需要快速、易于使用、综合和廉价的诊断设备，以检测传染病病原，即细菌、病毒。在此应用中，“晶体管实验室”的开发提出了细胞捕获和热裂解，以及在硅晶体管上进行核酸扩增的超快速技术，并对扩增产物进行直接、快速的电检测。将解决使核酸扩增真正成为即时检测的巨大挑战，在硅传感器阵列上，可以在不到5分钟的时间内获得高精度和可靠性的结果。为了应对这些挑战，单核细胞增生李斯特菌将在三年内被用作模型系统，但该技术平台也可以应用于其他病原微生物。智力优势：提出开发“晶体管实验室”的概念。具有以下智力优点；(a)利用微流体通道内的介质电泳，将单个细菌以线性阵列集中在单个场效应晶体管上。然后探讨了利用交流电压对场效应传感器表面进行超局部加热的方法。使用这种方法，附着在晶体管表面的细菌将在达到95℃或更高的温度下进行热裂解，(b)相同的传感器将用作加热器，使用聚合酶链反应或滚动电路扩增法进行核酸扩增反应，以及(c)探索使用晶体管本身进行PCR产物的无标签电检测。广泛影响：提议的工作将对硅基生物传感器领域产生广泛影响，提议的技术可以为开发护理点传感器提供重大进展。研究生将参加在伊利诺伊大学微与纳米技术实验室举办的暑期讲座和实践研讨会。REU将要求在夏季期间雇用更多的本科生与研究生一起研究项目，这也将有助于为未来发展研究生研究人员的管道。

The crisis in the management of infectious disease for the developed world and in the developing world (global health arena) requires rapid, easy to use, integrated, and inexpensive diagnostic devices for the detection of agents of infectious diseases, i.e. bacteria, viruses. In this application, the development of a ?Lab-on-a-Transistor? is proposed for cell capture and thermal lysing, and ultra rapid techniques for performing nucleic acid amplification on silicon transistors with a direct, rapid electrical detection of the amplified products. The grand challenge of making nucleic acid amplification truly a point-of-care test will be addressed, where the results can be obtained with high accuracy and reliability in less than 5 minutes on a silicon sensor array. To address these challenges, the bacteria Listeria monocytogenes will be used as the model system within the three years of this proposed grant but the technology platform can be applied to other pathogenic microorganisms as well. Intellectual Merit: The proposed concept of developing a ?Lab-on-a-Transistor? has the following intellectual merit; (a) concentrating single bacteria on individual field effect transistors with in a linear array using dielectrophoresis within a microfluidic channel. Then ultra-localized heating on the surface of the field effect sensor using an ac voltage will be explored. Using this method, thermal lysing of bacteria that are attached on the surface of the transistors will be performed by achieving temperatures of 95oC or higher, (b) the same sensor would be used as a heater to perform nucleic acid amplification reactions using either a polymerase chain reaction or a rolling circuit amplification method, and (c) exploring the use of the transistors themselves for label free electrical detection of the PCR products. Broad Impact: The proposed work will have a broad impact in the area of silicon based biosensors and the proposed technology could provide significant advances in developing point of care sensors. Graduate students will be involved in summer lecture and hands-on workshops to be held at the Micro and Nanotechnology Laboratory at the University of Illinois. REU summer support will be requested for hiring additional undergraduates to work with the graduate students on the research project during the summer, which will also help to develop a pipeline of graduate student researchers for the future.