SHF: Small: Development and Manufacturing Integrated DNA Circuits

电子计算机极大地提高了信息处理的效率，使工业过程自动化成为可能。然而，这种计算机在处理包括医疗诊断和治疗在内的生物医学任务时存在局限性。为了识别和处理生物输入，如DNA、蛋白质和小生物分子，电子计算机需要将化学输入转化为电子输出的化学传感器中间体。由于电脑是由非生物相容性和不可生物降解的材料制成的，因此很难植入人体。如果计算机是由生物相容性材料制成的，计算技术的生物医学应用将进入另一个维度。这种计算机可以通过识别和自主分析生物化学疾病标记的复杂组合来进行即时诊断测试，这将促进医疗诊断，使其更加准确和负担得起。此外，这样的计算机将有助于制造分子机器人——一种纳米级的设备，它可以感知人体内的生物标记，诊断疾病并迅速解决它，这将帮助医生对抗癌症和病毒感染等毁灭性疾病。DNA作为一种构建分子计算装置的材料引起了越来越多的关注。它的并行数据处理能力和沃森-克里克碱基配对的可预测性为利用DNA构建计算机和分子机器人提供了一个迷人的机会。此外，这些装置的生物相容性，以及以前开发的基因治疗方法，将使它们能够应用于癌症、传染病和遗传疾病的诊断和治疗。该项目的长期目标是构建一个基于DNA逻辑门的分子级处理器，并将其应用于解决生物医学挑战。在这个项目中，PI建议在开发第一台DNA计算机的过程中解决以下技术挑战：(i)创建多层集成电路（DNA纳米芯片）；（ii）通过共价交联稳定DNA纳米芯片。此外，PI将开发DNA纳米芯片，以解决一个实际意义重大的生物医学问题：癌症标记的识别，这有望激发人们对DNA计算的兴趣。建议的发展将通过创建一个易于使用的构建工具包来展示，用于构建集成DNA电路，可用于教育和外展项目。这些工具包的实用性将在实验室环境中与奥兰多当地一所高中的高中生合作进行测试。该奖项反映了美国国家科学基金会的法定使命，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。

Electronic computers have dramatically increased the efficiency of information processing and enabled automation of industrial processes. Such computers, however, have limitations when applied to address biomedical tasks including medical diagnostics and therapy. To recognize and process biological inputs, such as DNA, proteins, and small biomolecules, electronic computers require chemical-sensor intermediates that convert a chemical input into an electronic output. Computers are hard to insert into a human body as they are made of non-biocompatible and non-biodegradable materials. Biomedical applications of computational technologies would get another dimension if computers are made from a biocompatible material. Such computers could operate in a point-of-care diagnostic test by recognizing and autonomously analyzing complex combinations of biochemical disease markers, which would facilitate medical diagnostics, making them more accurate and affordable. In addition, such computers would help building molecular robots -- nanometer-scale devices that can sense biological markers inside human body to diagnose a disorder and promptly address it, which would help doctors fight such devastating diseases as cancer and viral infections, among others.DNA has attracted growing attention as a material for constructing molecular computational devices. Its parallel data-processing capabilities and predictability of Watson-Crick base pairing poses a fascinating opportunity for building computer and molecular robots from DNA. Moreover, biocompatibility of such devices, as well as previously developed approaches for gene therapy, would enable their applications in diagnostics and treatment of cancer, infectious and genetic diseases. The long-term goal of this project is to construct a molecular-scale processor based on DNA logic gates and apply it to address biomedical challenges. In this project, PI proposes to address the following technological challenges in a quest to the develop a first DNA computer: (i) create multilayered integrated circuits (DNA nanochips); and (ii) stabilize DNA nanochips by covalent cross-link. In addition, the PI will develop DNA nanochips to solve a practically significant biomedical problem: recognition of cancer markers, which is expected to stimulate interest in DNA computation. The proposed developments will be showcased by creating a user-friendly construction kit for building integrated DNA circuits, which can be used in educational and outreach projects. The practical utility of the kits will be tested in laboratory settings in collaboration with high-school students from a local Orlando high school.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.