Enabling study of electrically transduced information from biomolecules with a low-cost, versatile measurement (Versametrics) system

摘要 大多数研究或检测生物分子的方法都依赖于光谱技术。虽然取得了很大的进步 是利用光谱学制作的，有大量的信息和能力可以通过电子 测量。例如，几十年来，理想的生物医学诊断设备是显而易见的 利用电换能器来允许与光学换能器相比体积更小的测量系统， 以及其他优点，如高灵敏度、易于多路复用和低成本。然而，实际的发展 电传导式生物传感技术的发展仍然缓慢，而且在很大程度上无效。一大专业 造成这种低迷发展的因素是许多有经验的生物医学进入的高门槛 研究人员致力于电子技术。正确研究生物分子的电刺激方面 或可兴奋的细胞--无论是为了提高对生物分子/细胞功能的理解，还是为了选择性的检测 用于诊断-需要数万至数十万美元的研究基础设施和高级 培训，通常是在电气工程方面，使许多最有经验的生物医学研究人员无法 做出贡献。此外，刻画过程缓慢而繁琐，对 不同的测试条件--加在一起，减缓了该领域的整体进展。需要的是一个更多的 易获得、经济实惠、多功能的电子表征系统，促进电子产品的研究 与生物分子相关的转导信息。 在这个第一阶段，我们建议建立一个多功能电子测量平台的技术可行性 (Versametrics DART)能够实现和加速电换能生物分子的研究 信息。我们的目标是开发DART系统，用于表征制造在 几乎任何衬底(例如玻璃、纸张、硅)和各种受控环境(例如液体、气体) 无需电极线键合，并有直观的软件控制平台支持。我们的 初步结果表明，DART系统可用于电监测 生物传感器在使用定制的原子力显微镜尖端进行主动讯问时，这可能是 在生物分子研究中以无数种方式功能化。基于从研究中收集的反馈 关于DART原型系统的社区(请参阅支持函)，我们将追求三个具体目标 满足所需的系统功能。具体目标1将为DART开发两个模块：引线键合- 用于快速装置安装/拆卸的免费模块，与几乎任何生物装置基板兼容；其次， 一种液体环境测量模块。具体目标2将是扩大电气测量能力 DART到三个分辨率为0.1PA的可路由电压源，以实现多路复用器的特性 具有独立门控的生物装置配置。具体目标3将是建立DART控制软件 对执行电气、电化学和其他定制生物分析具有指导意义和直观性 测量。这些目标的成功将产生一个多功能的描述平台，它将克服 研究和开发生物分子电信号转换技术的长期障碍。

ABSTRACT Most approaches to studying or detecting biomolecules rely on spectroscopic techniques. While much progress has been made using spectroscopy, there is a wealth of information and capabilities available via electrical measurements. For instance, it has been clear for decades that the ideal biomedical diagnostic device would utilize electrical transduction to allow for a less bulky measurement system compared to optical transduction, along with other benefits such as high sensitivity, ease of multiplexing, and low cost. Yet, the actual development of electrically transduced biosensing technologies remains slow and has been largely ineffective. One major contributing factor to this sluggish development is the high barrier to entry for many experienced biomedical researchers to work on electronic technologies. To properly study electrically stimulated aspects of biomolecules or excitable cells – whether for improving understanding of biomolecular/cellular function or selective detection for diagnostics – requires tens to hundreds of thousands of dollars in research infrastructure and advanced training, typically in electrical engineering, leaving many of the most experienced biomedical researchers unable to contribute. In addition, the characterization process is slow and cumbersome, with limited adaptability to different testing conditions – altogether, slowing the overall progress in the field. What is needed is a more accessible, affordable, and versatile electronic characterization system to spur the research of electrically transduced information related to biomolecules. In this Phase I STTR, we propose to establish technical feasibility for a versatile electronic measurement platform (the Versametrics Dart) capable of enabling and accelerating research of electrically transduced biomolecular information. The objective is to develop the Dart system for characterizing electronic biochips fabricated on virtually any substrate (e.g., glass, paper, silicon) and in a variety of controlled environments (e.g., liquid, gas) without the need for electrode wire-bonding and supported by an intuitive software control platform. Our preliminary results demonstrate the utility of the Dart system for electrically monitoring the response of a biosensor while under active interrogation with a customized atomic force microscopy tip, which could be functionalized for biomolecular studies in countless ways. Based on feedback gathered from the research community regarding a prototype Dart system (see Letters of Support), we will pursue three specific aims to address needed system capabilities. Specific aim 1 will be to develop two modules for the Dart: a wire bonding- free module for rapid device installation/removal compatible with virtually any biodevice substrate and, secondly, a liquid environment measurement module. Specific aim 2 will be to expand the electrical measurement capacity of Dart to three routable voltage sources with 0.1 pA resolution to enable characterization of multiplexed biodevice configurations with independent gating. Specific aim 3 will be to establish Dart control software that is instructive and intuitive for performing electrical, electrochemical, and other custom bioanalytical measurements. Success in these aims will yield a versatile characterization platform that overcomes longstanding hurdles to studying, and developing technologies from, electrically transduced biomolecular signals.