Collaborative Research: Ionic Amplifiers for Biosensing

自然界已经进化出复杂的途径来放大检测到的低浓度离子或分子的信号。一个坚固的人造放大器系统，具有与自然中实现的对离子和分子信号的类似控制和放大，将有助于探测具有超低电导的生物通道(如那些在糖尿病中重要的通道)和了解生物过程。受生物学启发，这项研究将致力于根据电子集成电路和自然S信号通路的原理，研制具有放大性能的离子电路的第一步。离子电路的原型将使用具有受控几何形状和表面化学作为构建块的纳米孔来制备。研究人员选择纳米孔作为构建块，因为生物细胞中的生物通道和孔创造了生物放大的第一步。跨学科项目将为研究生和本科生创造一个良好的培训环境。两所大学当地学校的学生还计划参观纳米技术和生物传感方面的实践活动。这项研究的首要目标是设计一种通用的离子放大路线，并为生物传感应用制造响应时间为毫秒的离子晶体管。包括氮化硅、聚合物薄膜和玻璃纳米管在内的各种材料中的纳米孔将通过调节其表面特征和几何形状来呈现离子晶体管。纳米多孔晶体管将是三个端子系统，其功能原理类似于基于半导体的晶体管。在所构建的离子体系中，负离子携带负电荷，而不是电子；阳离子携带正电荷，而不是空穴。由于只有几个离子或分子的运动会导致测量信号的变化，因此需要系统的纳米尺度来实现快速的时间响应。将两个离子晶体管连接在一个电路中将导致制备一个相当于达林顿放大器的离子晶体管，其中电流增益等于两个分量晶体管放大的乘积。还将演示达林顿放大器在探测超低电导离子通道中的应用。还将探索离子差分放大器的制备。有了这些放大器，原则上可以实现千倍放大，使测量毫微微安培电流成为可能。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Nature has evolved complex pathways to amplify the signal from the detection of low concentrations of ions or molecules. A robust, man-made amplifier system with similar control and amplification of ionic and molecular signals as those achieved in Nature will be helpful for probing biological channels with ultra-low conductivities (like those important in diabetes) and understanding biological processes. Inspired by biology, this research will focus on development of the first steps to prepare ionic circuits with amplifying properties built on the principles of both electronic integrated circuits and Nature?s signaling pathways. Prototypes of ionic circuits will be prepared using nanopores with controlled geometry and surface chemistry as the building blocks. The investigators chose nanopores as building blocks, because biological channels and pores in a biological cell create the first step of biological amplification. The interdisciplinary program will create an excellent training environment for graduate and undergraduate students. Visits of students from local schools at both universities are also planned with hands-on activities on nanotechnology and biosensing.The overarching goal of the research is to design a generic route for ionic amplification and building ionic transistors with millisecond response time for biosensing applications. Nanopores in various materials including silicon nitride, polymer films and glass nanopipettes will be rendered ionic transistors by tuning their surface characteristics and geometries. The nanoporous transistors will be three terminal systems, which will function according to principles similar to those of semiconductor-based transistors. In the ionic systems constructed, instead of electrons, anions will carry negative charge, and, instead of holes, cations will carry positive charge. Nanoscale dimensions of the system are required for a quick temporal response, as movement of only a few ions or molecules will lead to changes in the measured signal. Connecting two ionic transistors in a circuit will lead to preparation of an ionic equivalent of a Darlington amplifier, where current gain is equal to a product of amplifications of the two component transistors. Application of the Darlington amplifier to probe ion channels with ultralow conductivities will be demonstrated as well. Preparation of an ionic differential amplifier will also be explored. With these amplifiers, in principle, thousand-fold amplification might be achieved, making measuring femto-Ampere currents accessible.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.