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Simulation and Fabrication of a New Novel 3D Injectable Biosensor for High Throughput Genomics and Proteomics in a Lab-On-a-Chip Device

机译:用于芯片实验室设备中高通量基因组学和蛋白质组学的新型新型3D可注射生物传感器的仿真和制造

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摘要

Biosensors are used for the detection of biochemical molecules such as proteins and nucleic acids. Traditional techniques, such as Enzyme-linked Immuno-sorbent Assay (ELISA) are sensitive but require several hours to yield an assay and usually require attaching a fluorophore molecule to the target molecule. Micromachined biosensors that employ electrical detection are now being developed. Here we describe one such device, which is ultrasensitive, real time, label-free and localized. It’s called the nanoneedle biosensor and shows promise to overcome some of the current limitations of biosensors. The key element about this device is a 10nm wide annular gap at the end of the needle, which is the sensitive part of the sensor. The total diameter of the sensor is about 100nm. Any change in the population of molecules in this gap results in a change of impedance across the gap. Single molecule detection should be possible because the sensory part of the sensor is in the range of bio molecules of interest. To increase throughput we can flow the solution containing the target molecules over an array of such structures, each with its own integrated readout circuitry to allow ‘real-time’ detection (i.e. several minutes) of label free molecules without sacrificing sensitivity. To fabricate the arrays we used electron beam lithography together with associated pattern transfer techniques. Preliminary measurements on individual needle structures in water are consistent with the design. Since the proposed sensor has a rigid nano-structure, this technology, once fully developed, could ultimately be used to directly monitor protein quantities within a single living cell, an application that would have significant utility for drug screening and studying various intracellular signaling pathways.
机译:生物传感器用于检测生化分子,例如蛋白质和核酸。传统技术,例如酶联免疫吸附测定(ELISA)是敏感的,但是需要数小时才能完成测定,并且通常需要将荧光团分子连接到目标分子上。现在正在开发采用电子检测的微机械生物传感器。在这里,我们描述了一种这样的设备,它是超灵敏,实时,无标签且本地化的。它被称为纳米针生物传感器,它有望克服目前生物传感器的某些局限性。该设备的关键要素是在针头末端的10nm宽的环形间隙,这是传感器的敏感部分。传感器的总直径约为100nm。该间隙中分子总数的任何变化都会导致间隙中的阻抗发生变化。单分子检测应该是可能的,因为传感器的感觉部分在感兴趣的生物分子范围内。为了增加通量,我们可以使包含靶分子的溶液流过一系列这样的结构,每个结构都具有自己的集成读出电路,从而可以在不牺牲灵敏度的情况下“实时”检测(即几分钟)无标记分子。为了制造阵列,我们使用了电子束光刻技术以及相关的图案转移技术。对水中单个针头结构的初步测量与设计一致。由于拟议的传感器具有刚性的纳米结构,因此该技术一旦得到充分开发,最终可用于直接监测单个活细胞内的蛋白质量,该应用将对药物筛选和研究各种细胞内信号通路具有重要的用途。

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