Collaborative Research: Ionic Amplifiers for Biosensing

自然界已经进化出复杂的途径来放大来自低浓度离子或分子检测的信号。 一个强大的人造放大器系统，具有与自然界中实现的类似的离子和分子信号的控制和放大，将有助于探测具有超低电导率的生物通道（如糖尿病中重要的生物通道）和理解生物过程。受生物学的启发，这项研究将集中在第一步的发展，以准备离子电路与放大性能建立在电子集成电路和自然的原则？的信号通路。离子电路的原型将使用具有受控几何形状和表面化学的纳米孔作为构建块来制备。研究人员选择纳米孔作为构建模块，因为生物细胞中的生物通道和孔创造了生物扩增的第一步。跨学科课程将为研究生和本科生创造一个良好的培训环境。此外，两所大学亦计划邀请本地学校的学生参观，并安排有关纳米技术及生物传感的实践活动。研究的首要目标是设计一条通用的离子放大路线，并建造响应时间为毫秒的离子晶体管，以应用于生物传感。通过调整各种材料的表面特性和几何形状，包括氮化硅、聚合物薄膜和玻璃纳米移液管中的纳米孔将成为离子晶体管。纳米多孔晶体管将是三端系统，其将根据类似于基于半导体的晶体管的原理起作用。在所构建的离子系统中，阴离子将携带负电荷而不是电子，阳离子将携带正电荷而不是空穴。纳米尺度的系统需要快速的时间响应，因为只有少数离子或分子的运动将导致测量信号的变化。在电路中连接两个离子晶体管将导致制备达林顿放大器的离子等效物，其中电流增益等于两个分量晶体管的放大率的乘积。应用达林顿放大器探测离子通道与超低电导率将被证明。离子差分放大器的制备也将进行探讨。通过这些放大器，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。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值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.