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

使用低成本、多功能测量 (Versametrics) 系统能够研究生物分子的电转换信息

• 批准号: 10324989
• 负责人: Aaron Franklin
• 金额: $ 24.96万
• 依托单位: VERSAMETRICS LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2023-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10324989
• 关键词: Address; Area; Atomic Force Microscopy; Biological; Biological Process; Biosensing Techniques; Biosensor; Cell physiology; Cells; Communities; Computer software; Controlled Environment; Custom; Detection; Development; Devices; Diagnostic; Electrical Engineering; Electrodes; Ensure; Environment; Equipment; Excision; Feedback; Gases; Glass; Infrastructure; Instruction; Intuition; Laboratories; Letters; Liquid substance; Measurement; Monitor; Optics; Paper; Phase; Process; Research; Research Infrastructure; Research Personnel; Resolution; Route; Scanning Probe Microscopes; Signal Transduction; Silicon; Small Business Technology Transfer Research; Software Design; Source; Spectrum Analysis; Structure; System; Techniques; Technology; Testing; Training; Work; base; biochip; cost; design; electrical measurement; equipment training; experience; improved; medical schools; micromanipulator; nanomaterials; printed circuit board; prototype; response; single molecule; success; usability; virtual; voltage

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.

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。很大进展 已经使用光谱学，有丰富的信息和能力，可通过电气 测量.例如，几十年来，人们已经清楚地认识到，理想的生物医学诊断设备应该 利用电转换以允许与光学转换相比体积较小的测量系统， 沿着其它优点，例如高灵敏度、易于多路复用和低成本。然而，实际发展 电转换生物传感技术的发展仍然缓慢，而且在很大程度上是无效的。一个主要 造成这种缓慢发展的一个因素是许多有经验的生物医学行业的进入壁垒很高， 研究人员致力于电子技术。为了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选择性检测 诊断-需要数万至数十万美元的研究基础设施和先进的 培训，特别是在电气工程，离开许多最有经验的生物医学研究人员无法 作出贡献.此外，表征过程缓慢且繁琐，对环境的适应性有限。 不同的测试条件-加在一起，减缓了该领域的整体进展。我们需要的是一个更 可访问的，负担得起的，多功能的电子表征系统，以刺激研究电 与生物分子相关的信息。 在第一阶段STTR中，我们建议建立多功能电子测量平台的技术可行性 (the Versametrics Dart）能够实现和加速电转换生物分子的研究 信息.目的是开发Dart系统，用于表征制造在生物芯片上的电子生物芯片。 实际上任何衬底（例如，玻璃、纸、硅）和在各种受控环境中（例如，液体、气体） 而不需要电极引线键合并且由直观的软件控制平台支持。我们 初步结果表明，实用的飞镖系统的电监测的响应， 生物传感器，同时在主动询问与定制的原子力显微镜尖端，这可能是 以无数种方式进行生物分子研究。根据从研究中收集的反馈， 关于原型Dart系统（见支持信），我们将追求三个具体目标， 满足所需的系统能力。具体目标1将是为Dart开发两个模块：引线键合- 用于快速装置安装/移除的自由模块，其与几乎任何生物装置基底相容，其次， 液体环境测量模块。具体目标2将是扩大电气测量能力 的Dart到三个可路由的电压源，分辨率为0.1 pA， 具有独立门控的生物设备配置。具体目标3将是建立飞镖控制软件， 对于执行电学、电化学和其他定制生物分析具有指导性和直观性 测量.这些目标的成功将产生一个通用的表征平台， 研究和开发来自电转换生物分子信号的技术的长期障碍。