EFRI-BioFlex: A Flexible Glucose Fuel Cell

该提案试图创建一个灵活的葡萄糖燃料电池和相关的超低功耗生物电子学，用于未来的自供电大脑植入物。柔性葡萄糖燃料电池能够使体积密度增加20倍，可从生物相容的1 cm（d）x 4 cm（l）设备获得320 uW的功率，该设备植入大脑和脊髓的蛛网膜下腔。因此，用于瘫痪的完全植入式大脑植入物具有用于神经记录、刺激、解码和无线通信的新型最先进的超低功耗电子器件，总共消耗95 uW，可以以3倍的安全系数供电，允许燃料电池输出随时间变化。本提案试图在大鼠体内测试一个具有完整功能的脑植入系统，该系统采用较小几何形状的3 mm（d）x 3 mm（l）器械，以确保慢性（6个月）长期生物相容性和性能符合我们的功率预算。使用脑脊髓液作为动力源，其具有低200倍的蛋白质计数和低近百万倍的细胞计数，以及仅低2倍的葡萄糖含量，提供了与血浆或间质液中的先前工作显著不同的新的植入部位。这种新型的预期植入部位沿着我们使用的材料和技术已被证明可以增加生物相容性，如Nafion封装，延长寿命。柔性葡萄糖燃料电池将使用众所周知的半导体制造技术在硅晶片上制造，从而实现制造可扩展性并易于与同一晶片上的电子器件集成。智力优势：这项工作结合了来自多个学科的创新和知识，有可能在医疗植入物领域创造一种改变范式的能力：1）以前的酶基葡萄糖燃料电池一直受到酶降解问题的困扰，这些问题导致它们在几个月后效率低下。非生物燃料电池更适合于长期慢性操作，但具有相对较低的功率输出。 非生物柔性葡萄糖燃料电池的创建将可用功率的体积密度增加了一个数量级以上，同时保留了长期非生物操作的益处。2)超低功耗生物电子技术的使用在大脑植入系统的各个方面都实现了最先进的性能，使微型葡萄糖燃料电池能够满足预期医疗应用所需的功率预算，甚至安全系数为3倍，并适合严格限制的身体空间。 3)标准半导体制造技术的使用使得能够以卷起的几何形状廉价地制造具有其自身的电源和电子器件的整个柔性医疗植入物，而不会像用柔性有机电子器件制成的系统那样牺牲性能。4)富含葡萄糖的脑脊髓液是高度非生物的（不含细胞）并且高度不含蛋白质，使其成为用于提供燃料而不引起电极生物污染的理想来源。这项工作可以使葡萄糖燃料电池在经过40年的研究后成为现实。更广泛的影响：葡萄糖燃料电池可用于治疗心律失常、糖尿病、癫痫、脑深部疾病和癌症肿瘤监测。卷起来？糖动力电池可用于非侵入式无线医疗监测或可穿戴和柔性电子系统。灵活的葡萄糖燃料电池可以帮助解决无毒（不像电池），可再生，碳中性，实用能源的国家挑战。PI计划引入体外葡萄糖燃料电池供电的ECG作为他在麻省理工学院生物电子学课程中的一个项目，该项目已在麻省理工学院教授了10多年。研究团队进一步计划开发一个模块，该模块将使用微流体设置来监测燃料电池输出电压下细胞中的输出蛋白质浓度，并将该平台引入实践。通过终身幼儿园和？科学星期六？在林肯实验室PI计划从他积极参与麻省理工学院计算和系统生物学，生物物理学，合成生物学和生物电努力的招生计划中招募代表性不足的学生。研究者将参加SEED（星期六工程丰富和发现）学院，该学院招收来自波士顿，剑桥和劳伦斯公立学校的学生;他们还将与女工程师协会（SWE）密切合作，吸引有前途的年轻女性进入生物医学和生物工程研究;而且，他们将积极与麻省理工学院夏季研究计划（MSRP），传统上包括代表性不足的学生进入研究计划。因此，该提案将产生广泛的技术影响，广泛的教育影响，并扩大社会参与。

This proposal attempts to create a flexible glucose fuel cell and associated ultra-low-power bioelectronics for self-powered brain implants of the future. The flexible glucose fuel cell enables a 20x increase in volumetric density with 320 uW of power available from a biocompatible 1cm (d) x 4 cm (l) device, which is implanted in the subarachnoid spaces of the brain and spinal cord. Thus, fully implantable brain implants for paralysis with novel state-of-the-art ultra-low-power electronics for neural recording, stimulation, decoding, and wireless communication, which consume 95 uW in total, can be powered with a safety factor of 3x that allows for fuel-cell output variation over time. This proposal attempts to test a fully functional brain-implant system in a smaller geometry 3 mm (d) x 3mm (l) device in a rat to ensure chronic ( 6 months) long-term biocompatibility and performance that meets our power budget. The use of the cerebrospinal fluid as a power source, which has a 200x lower protein count, and almost million-fold lower cell count, and only a 2x lower glucose content, provides a novel site for implantation significantly different from prior work in blood plasma or interstitial fluid. This novel intended site of implantation along with our use of materials and techniques that have been proven to increase biocompatibility, such as Nafion encapsulation, enhance longevity. The flexible glucose fuel cell will be fabricated using well-known semiconductor fabrication techniques on a silicon wafer enabling manufacturing scalability and ease of integration with electronics on the same wafer. Intellectual Merit: This work combines innovations and knowledge from several disciplines to potentially create a paradigm-changing capability in the field of medical implants: 1) Prior enzyme-based glucose fuel cells have been plagued by enzyme-degradation issues that have led them to be inefficient after a few short-term months. Abiotic fuel cells are more suited for long-term chronic operation but have relatively low power outputs. The creation of an abiotic flexible glucose fuel cell increases the volumetric density of available power by more than an order of magnitude while preserving the benefits of long-term abiotic operation. 2) The use of ultra-low-power bioelectronics that achieves state-of-the-art performance in all aspects of a brain-implant system enables miniature glucose fuel cells to meet the power budget needed for intended medical applications with even a safety factor of 3x and to fit within tightly constrained body spaces. 3) The use of standard semiconductor fabrication techniques enables entire flexible medical implants with their own power source and electronics to be cheaply fabricated in a rolled-up geometry without sacrificing performance as in systems made with flexible organic electronics. 4) The glucose-rich cerebrospinal fluid is highly abiotic (free of cells) and highly protein free making it an ideal source for providing fuel while not causing electrode bio-fouling. This work could enable glucose fuel cells to become practical after four decades of research.Broader Impact:Glucose fuel cells have use in the treatments of cardiac arrhythmia, diabetes, epilepsy, deep brain disorders, and cancer tumor monitoring. Rolled-up ?sugar powered batteries? may be used in non-invasive wireless medical monitoring or in wearable and flexible electronic systems. The flexible glucose fuel cell can help solve a national challenge for non-toxic (unlike batteries), renewable, carbon-neutral, energy sources that are practical. The PI plans to introduce an in-vitro glucose-fuel-cell powered ECG as a project in his course in bioelectronics at MIT that has been taught for over 10 years at MIT The Research Team further plans to develop a module that will use microfluidic setup to monitor output protein concentrations in cells at the fuel-cell output voltages and introduce the platform to the do-it-yourself community at MIT through programs such as Lifelong Kindergarten and ?Science Saturday? at Lincoln Lab. The PI plans to recruit under-represented students from his active participation in the admissions programs of the Computational and Systems Biology, Biophysics, Synthetic Biology, and Bioelectrical endeavors at MIT. The investigators will participate in SEED (Saturday Engineering Enrichment and Discovery) Academy, which enrolls students from Boston, Cambridge, and Lawrence Public Schools; they will also work closely with the Society of Women Engineers (SWE) to attract promising young women into biomedical and bioengineering research; and, they will work actively with the MIT Summer Research Program (MSRP), which has traditionally included underrepresented students into research programs. Thus the proposal will have broad technical impact, broad educational impact, and broaden societal participation.