IIBR Instrumentation: Collaborative Research: Development of a Single-Biomolecule Detection Instrument via Digital Counting of Nanoparticles

阿克伦大学和宾夕法尼亚州立大学被授予创造一种数字仪器，用于快速检测具有单分子分辨率的广泛的生物分子。这种高度跨学科的研究将满足许多生物学研究领域对低丰度生物分子检测的迫切需求，并为参与该项目的学生提供良好的教育经验。设计理念和数字仪器将纳入本科生和研究生课程。学生将通过接触基本的工程/科学原理和实践经验，接受培训并为下一代工程师和研究人员所需的专业知识做好准备。研究活动也将为本科生和K-12学生提供极好的培训机会。通过多项教育和外展计划，如UA的“高中桥”、“增加工程学术人员的多样性”和“女性参与工程”计划，以及PSU的“多元文化工程计划”、“探索大学计划”和“壮观的科学活动”计划，我们将招收本科生和初中/高中生，重点是代表性不足的学生和女性学生，参与拟议的研究活动。其目标是通过与经验丰富的研究人员的互动，将学习环境扩展到课堂之外，激发学生的兴趣，并提高学生在STEM领域的留存率。拟议的教育和外联活动将有助于在俄亥俄州和宾夕法尼亚州这两个美国锈带州培育高科技环境，并通过科学教育直接影响高科技产业的振兴。该仪器有望推进细胞和分子生物学研究，并成为俄亥俄州东北部、宾夕法尼亚州和全国科学界的有用工具。其他社会效益包括改善生物防御、保护环境和促进疾病诊断和预后。拟议的仪器将推动生物分子检测领域的以下创新和能力。首先，通过分子识别的独特设计的微柱盒，可以将生物分子的测量转换为数字信号。数字计数不需要繁琐的校准曲线，也不涉及信号衰减。因此，测量将更加稳健和可靠。其次，一个目标生物分子原则上可以用一个数字尖峰来表示，这在单分子分辨率下对超低丰度生物分子的数字检测具有很大的潜力。这种超高分辨率和数字化能力是目前最先进的方法难以实现的。第三，该仪器将是一个很有前途的通用平台，用于检测广泛的生物分子。第四，该仪器将能够使用多个墨盒同时快速检测多个生物分子。第五，传感器将具有较长的保质期，并允许现场应用，因为这些传感器可以承受恶劣的环境。目前还没有具备这些独特功能的仪器。这种灵敏的仪器为从小尺寸样品中分析各种生物分子带来了巨大的希望。因此，它可以用于推进许多生物学研究领域，包括但不限于细胞信号、干细胞生物学、神经科学、组织工程和细胞代谢。该奖项反映了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。

An award is made to University of Akron and Pennsylvania State University to create a digital instrument for rapid detection of a broad range of biomolecules with single-molecule resolution. The highly interdisciplinary research will fulfill the urgent needs of low-abundance biomolecules detecting in many biological research areas and provide excellent educational experiences for the students involved in the project. The design concept and the digital instrument will be incorporated into undergraduate and graduate courses. The students will be trained and prepared with the expertise needed for the next generation of engineers and researchers by being exposed to the underlying engineering/science principles and hands-on experiences. The research activities will also provide excellent training opportunities for undergraduates and K-12 students. Through multiple education and outreach programs such as "High School Bridge", "Increasing Diversity in Engineering Academics" and "Women in Engineering" programs at UA, and "Multicultural Engineering Program", "Exploration U Programs", and the "Spectacular Science Event" programs at PSU, we will recruit undergraduate and middle/high school students, with an emphasis on underrepresented and female students, to participate in the proposed research activities. The goal is to extend the learning environment beyond the classroom, motivate the student interests and improve the retention in STEM fields via interacting with experienced researchers. The proposed education and outreach activities will help cultivate a high-tech environment in Ohio and Pennsylvania, two of the rust-belt states in the nation, and directly impact revitalization of high-tech industry through science education. This instrument is expected to advance cellular and molecular biology research, and become a useful tool for the scientific communities in Northeastern Ohio, Pennsylvania and the nation. Other societal benefits include improving biodefense, protecting the environment and facilitating disease diagnosis and prognosis.The proposed instrument will advance the field of biomolecule detection for the following innovations and capabilities. First, with the unique design of micropillar cartridges through molecular recognition, measurement of biomolecules can be converted to digital signals. The digital counting does not need tedious calibration curves or involve signal decay. Thus, the measurement will be more robust and reliable. Secondly, one target biomolecule can in principle be represented by one digital spike, which holds great potential for digital detection of biomolecules of ultra-low abundance, at single-molecule resolution. This ultra-high resolution and digitization capability are difficult to achieve with current state-of-the-art methods. Thirdly, this instrument will be a promising universal platform for detecting a broad range of biomolecules. Fourthly, this instrument will enable rapid detection of multiple biomolecules simultaneously by using multiple cartridges. Fifthly, the sensors will have a long shelf life and allow for field applications since the sensors are tolerant of harsh environments. An instrument with these unique capabilities is currently unavailable. This sensitive instrument holds great promise for the analysis of various biomolecules from small-size samples. Thus, it can be utilized to advance many biological research areas including, but not limited to, cell signaling, stem cell biology, neuroscience, tissue engineering, and cell metabolism.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.