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

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.PROJECT NARRATIVE There is a wealth of information available through the electrical study of biomolecules, whether it be their function and structure for understanding biological processes or their presence and concentration for diagnostic purposes. Unfortunately, the barriers to entry for biomedical researchers to pursue electrical measurements have been significant in terms of costly equipment and training. This Phase I STTR project seeks to develop a standalone, intuitive system – the Versametrics Dart – that will enable biomedical researchers from virtually any background to pursue electrical characterization of all varieties of biochips, thus accelerating and expanding progress in this field.