Minimal DNA Nanopores for Electrical Sensing of Proteins

蛋白质在我们的生活中至关重要。它们执行我们身体的主要功能，控制我们的运动、能量转换、免疫防御和思维。在医学上，功能异常的蛋白质引起疾病。然而，这些蛋白质可以被药物靶向治疗细胞。酶在低成本合成药物分子或织物的节能清洁方面也具有重要的生物技术意义。检测和分析蛋白质是预测疾病、开发治疗方法和为工业设计蛋白质的第一步。对蛋白质的分析提高了我们对其结构、动力学和功能的理解。理想情况下，蛋白质的传感应该是简单和快速的，并使用廉价和便携式设备进行。这提高了研究效率，并在诊断和国土安全方面开辟了护理点传感。该项目将提供一种新的方法，以一种便携而科学准确的方式来感知蛋白质，从而克服现有方法的问题。传统的方法存在一些问题，比如需要用荧光标记来标记蛋白质，这可能会干扰蛋白质的结构和功能。光学检测也会增加分析设备的重量和成本。传统传感方法的另一个限制是，它们平均超过数百万个分子，很难检测到生物学上重要的亚群。我们将开发一种新的方法，以标签和无光学的电子方式感知蛋白质，使用便携式设备，能够将蛋白质揭示到单个分子的水平。该策略目前被用于DNA链测序。我们的行业合作伙伴牛津纳米孔技术公司开发了一种手持式基因组测序设备。当单个链通过薄膜上的纳米级孔时，可以检测到分析物。孔隙的暂时阻塞改变了电子读出信号，类似于当石头在管内时水流的减少。我们将能够感知到足够宽以容纳蛋白质的蛋白质。新的孔将由DNA支架组成，从而利用DNA的精湛能力作为纳米级建筑材料。化学改性将是实现孔隙功能性能的关键。为了使学术界、工业界和社会的利益最大化，我们将与我们的商业伙伴密切合作，测试便携式电传感设备中的新孔隙。

Proteins are of paramount importance in our lives. They carry out the main functions in our bodies and control our movement, energy conversion, immune defence, and thinking. In medicine, functionally aberrant proteins cause disease. The proteins can, however, be targeted by drugs to cure cells. Enzymes are also of biotechnological importance in the cost-efficient synthesis of drug molecules or for the energy-saving cleaning of fabrics.Detecting and analysing proteins is the first step towards predicting diseases, developing cures, and engineering proteins for industry. The analysis of proteins improves our understanding their structure, dynamics, and function. Ideally, sensing of proteins should be simple and fast and be conducted using inexpensive and portable equipment. This increase research efficiency and opens up point-of-care sensing in diagnosis and homeland security.This project will provide a new way to sense proteins in a portable yet scientifically accurate fashion thereby overcoming problems of existing approaches. Classical approaches have issues such as the requirement to label the proteins with a fluorescent tag which can interfere with the structure and function of the proteins. Optical detection can also increase the weight and cost of the analytical device. Another limitation of conventional sensing approaches is that they average over millions of molecules and have difficulties to detect biologically important sub-groups.We will develop a new approach to sense proteins in a label and optics-free electrical fashion using portable equipment capable of uncovering proteins down to the level of individual molecules. The proposed strategy is currently being used for DNA strand sequencing. Our industry partner Oxford Nanopore Technologies has developed a hand-held device for genome sequencing. The analytes are detected when individual strands pass through nanoscale pores in a thin membrane. The temporary blockade of the pores alters the electronic read-out signal similar to the reduction of water flow when a stone is inside a tube. We will be able to sense proteins which are wide enough to accommodate proteins. The new pores will be composed of DNA stands, thereby exploiting the exquisite ability of DNA to function as a nanoscale construction material. Chemical modification will be key to achieve the functional performance of the pores. To maximise the benefit for academia, industry and society, we will strongly collaborate with our commercial partner to test the new pores in the portable electrical sensing devices.