Piezoresistive Sensing Platform for High-Throughput Single Platelet Nanomechanics

用于高通量单血小板纳米力学的压阻传感平台

• 批准号: 1711259
• 负责人: Oliver Brand
• 金额: $ 33万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1711259&HistoricalAwards=false
• 关键词: Piezoresistive; Sensing; Platform; Throughput; Single

Abnormal clotting and bleeding are the cause, or a lethal complication, of many diseases including heart disease, stroke, and cancer. During the formation of blood clots, biochemically activated platelets interact with growing networks of fibrin polymers and contract against this fibrin scaffold. Today, few tools exist to predict when a person may experience abnormal clotting or bleeding, and nearly all of these tools rely on sensing biochemicals associated with clot formation or breakup. However, new research has shown that changes to the physical forces nominally applied by platelets are associated with bleeding. Rather than attempting to sense trace amounts of biochemicals associated with clotting, the ultimate goal of this project is, thus, to examine platelet forces to predict abnormal bleeding and clotting. The physical strength of a cell may be directly linked to bleeding and clotting, thus representing a potentially "disruptive" paradigm of biophysical testing that could be applied to many other diseases. While promising, this novel approach requires assaying a large population of platelets to gain clinically relevant data and predict bleeding and clotting disorders. Using today's technologies, which are mostly utilizing microscopy-based optical techniques, this still requires too much time to be useful in the clinic. To overcome the limitations of optical techniques to measure platelet forces, this proposal seeks to explore non-optical transduction mechanisms to create a rapid, high-throughput platform capable of assaying large numbers of individual platelets. More specifically, the goal of this project is to develop piezoresistive sensing platforms for high-throughput mechanical testing of single blood platelets. Using piezoresistive transducers for force sensing, the proposed platforms will overcome the key bottleneck to high-throughput single-cell force analysis with all existing techniques, namely their reliance on optical imaging. The two proposed sensing platforms are based on arrays of microdots and nanopillars and mimic the two most common optical platforms for cell force measurements, traction force microscopy and microfabricated post array detectors, respectively. Thereby, the contraction force exerted by a blood platelet on a pair of microdots is measured with underlying sub-micrometer strain gauges, while the platelet-contraction-induced deflection of nanopillars is sensed by stress-sensitive metal-oxide-semiconductor field effect transistors (MOSFET) embedded into the underlying substrate. On the sensing system side, the intellectual merit lies in the design and fabrication of large arrays of piezoresistive force sensors with nano-Newton force resolution in an ultra-small form factor, targeting a pitch for the microdot/pillar pairs of less than 15µm.

异常凝血和出血是许多疾病的原因，或致命的并发症，包括心脏病，中风和癌症。在血凝块的形成过程中，生物化学活化的血小板与纤维蛋白聚合物的生长网络相互作用，并与该纤维蛋白支架收缩。今天，很少有工具可以预测一个人何时会出现异常凝血或出血，几乎所有这些工具都依赖于检测与凝块形成或破裂相关的生化物质。然而，新的研究表明，血小板名义上施加的物理力的变化与出血有关。因此，该项目的最终目标不是试图检测与凝血相关的微量生化物质，而是检查血小板力以预测异常出血和凝血。细胞的物理强度可能与出血和凝血直接相关，因此代表了生物物理测试的潜在“破坏性”范例，可应用于许多其他疾病。虽然很有前途，但这种新方法需要测定大量血小板，以获得临床相关数据并预测出血和凝血障碍。使用今天的技术，主要是利用基于显微镜的光学技术，这仍然需要太多的时间才能在临床上有用。为了克服光学技术测量血小板力的局限性，该提案旨在探索非光学转导机制，以创建一个快速，高通量的平台，能够测定大量的个体血小板。更具体地说，该项目的目标是开发压阻传感平台，用于单血小板的高通量机械测试。使用压阻式传感器进行力传感，所提出的平台将克服所有现有技术的高通量单细胞力分析的关键瓶颈，即它们对光学成像的依赖。这两个拟议的传感平台是基于阵列的微点和纳米柱和模仿两个最常见的光学平台的细胞力测量，牵引力显微镜和微加工后阵列检测器，分别。因此，由血小板施加在一对微粒上的收缩力用下面的亚微米应变计测量，而血小板收缩引起的纳米柱偏转由嵌入到下面的衬底中的应力敏感金属氧化物半导体场效应晶体管（MOSFET）感测。在传感系统方面，其智力优势在于设计和制造具有纳牛顿力分辨率的大型压阻式力传感器阵列，其外形尺寸超小，目标是小于15µm的微点/柱对间距。

项目成果

Nanofabrication for all-soft and high-density electronic devices based on liquid metal

• DOI: 10.1038/s41467-020-14814-y
• 发表时间: 2020-02-21
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Kim, Min-gu;Brown, Devin K.;Brand, Oliver
• 通讯作者: Brand, Oliver

Creating Social Value via Undergraduate Design Thinking Course with K-12 STEM Education Outreach in Various Community Settings

通过本科生设计思维课程创造社会价值，并在各种社区环境中开展 K-12 STEM 教育推广

• DOI: 10.1007/s43683-022-00064-5
• 发表时间: 2022
• 期刊: Biomedical Engineering Education
• 作者: Hardy, Elaissa T.;Fulmer, Sara Ivey;Le Doux, Joseph M.;Lam, Wilbur A.
• 通讯作者: Lam, Wilbur A.

Submicrometer-Scale All-Soft Electronics Based on Liquid Metal

基于液态金属的亚微米级全软电子器件

• DOI: 10.1109/transducers.2019.8808502
• 发表时间: 2019
• 期刊: Actuators and Microsystems & Eurosensors XXXIII (TRANSDUCERS & EUROSENSORS XXXIII
• 作者: Kim, Min-gu;Brown, Devin K.;Brand, Oliver
• 通讯作者: Brand, Oliver